Title of Invention

REGIIOSELECTIVE FLUORINATION OF PHENYL-SUBSTITUTED TRIAZOLINONES

Abstract A process for the preparation of a 3, 4-disubstituted -l-(4-substituted-2-fluorophenyl-l,2,4-triazolin-5-one compound of the Formula I wherein: X is hydrogen, halogen, Ci-C6-alkyl, Ci-C6-haloalkyl, or nitro; and R and R* are independently hydrogen, halo, Ci-C6-alkyl, C2-C6-alkenyl, C3- Cs.-alkynyl, Ci-C6-haloalkyl, C2-C6-haloalkenyl, C2-C7-acyl, C2-C6- alkoxyalkyl, C2-C6-cyanoalkyl, Ci-C3-alkylsulfinyl, Ci-C3-alkylsulfonyl, or Ci-Cs-alkylthio-Ci-Cs-alkyl; the process comprising the step of treating a compound of the Formula II with a fluorinating agent at a temperature of from 60° to 120°C in the presence of an organic solvent to form a compound of the Formula I; wherein: X and R are as defined above: and R' is independently an alkali metal cation, hydrogen, halo, Ci-C6-alkyl, C2- Ce-alkenyl, C3-Cs-alkynyl, Ci-Ce-haloalkyl, C2-C6- haloalkenyl, C2-C7-acyl, C2-C6-alkoxyalkyl, C2-C6-cyanoalkyl, Ci-C3-alkylsulfmyl, Ci-C3-alkylsulfonyl, or Ci-Cs-alkylthio^Ci^C^alkyl.
Full Text FORM 2
THE PATENTS ACT, 1970
[39 OF 1970]
COMPLETE SPECIFICATION
[See Section 10; Rule 13]
"A process for the preparation of a 3, 4-disubstituted -l-(4-substituted-2-fluorophenyl-l,2,4-triazolin-5-one compound of Formula I"
FMC CORPORATION, of 1735 Market Street, Philadelphia, Pennsylvania, 19103, United States of America,
The following specification particularly describes the nature of the invention and the manner in which it is to be performed:-




This application claims benefit of U.S. Provisional Application No. 60/098,060, filed August 27, 1998.
The present invention relates generally to processes for preparing l-(2-fluorophenyl)-substituted triazolinones. In particular, it pertains to the fiuorination of the phenyl ring of 4,5-dihydro-l-(4-substituted phenyl)-3,4-disubtituted-l,2,4-triazol-5(lH)-ones.
The 4,5-dihydro-l-(2-fluoro substituted phenyl)-3,4-disubtituted-l,2,4-triazol-5(lH)-ones, for example 4,5-dihydro-l-(4-cM'oro'2-fluorophenyl)-3-methyl-4--diflupromethyl-l,'2,4-triazol-5(lH)-one, are critical intermediates in the manufacture of fine chemicals, such as pesticides. For example, 4,5-dihydro-l-(4-chloro-2-fluorophenyl)-3-methyl-4-difluoromethyl-l,2,4-triazol-5(lH)-one is a known intermediate in the manufacture of the herbicide ethyl a-2-dichloro-5-[4-(difluoromethyl)-4,5-dihydro-3-methyI-5-oxo-lH-l,2,4-triazol-lyl]-4-fluorobenzenepropanoate.
Fiuorination of complex aromatic systems is difficult because of fluorine's high reactivity. As a result, there are only a few practical commercial methods by which fluorine can be introduced regioselectively into complex aromatic systems.
One method of fiuorination includes the Balz-Schiemann reaction in which an aromatic ring is fluorinated by the thermal decomposition of diazonium fluoroborates. This method has failed to provide the desired product in appreciable yield.
Another method for the preparation of fluorinated complex aromatic systems, in particular phenyl-substituted triazolinones, includes the use of 2-fluoroaniline or 2-fluorophenylhydrazine as
-2-

WO 00/12490 _P£IZL—
starting materials for the preparation of a corresponding l-(2-fluorophenyl)-substituted triazolinones thereby avoiding the difficult task of fluorinating adeactivated aromatic ring. These procedures provide low synthetic yields.
Electrophilic NF fluorinating agents have been used to directly fluorinate mono substituted and disubstituted aromatics to provide mixtures of the ortho- and para- fluoro-phenyl substituted compounds. (J/^yem. Soc, Chem. Commun., 1992, pg. 595-596) Substantially isomerically pure para-fluoro-trisubstituted aromatic rings have been prepared with this procedure when at least one of the substituents of the disubstituted aromatic starting material is electron donating. This procedure has not been applied to the preparation of l-(2-fluoro-4-subsu^ted-pnhenyJ)-3,4«disubstituted triazolinones.
There remains a need for a simple and generally high yielding method for the preparation of the key synthetic intermediates l-(2-fiuoro-4-substituted-phenyl)-3,4-disubstituted triazolinones in substantially isomerically pure or isomerically enriched form using l-(4-substituted-phenyl)-3,4-disubstituted triazolinones as starting materials.
SUMMAKfOF THE INVENTION
g*. —
The present invention.proxldes^^ajgaethod by which fluorine can be regioselectively introduced into complex aromatic systems. The present invention provides a method for the preparation of 4,5-dihydro-l-(2-fluoro-4-substituted phenyl)-3,4-disubtituted-1,2,4-triazol-5(lH)-one of the Formula I below by the direct fluorination of a corresponding 4,5-dihydro-l-(4-substituted phenyl)-3,4-
-3-




disubstituted-l,2,4-triazol-5(lH)-one of the Formula II with a fluorinating agent in the presence of an organic solvent.
(^The present invention provides a high degree of regioselectivity in the fluorination of complex aromatic systems by preferentially fluorinating the pendant phenyl group of the compound of the Formula II at the ortho-position rather than the meta- or para-positions. Treatment of a compound of the Formula II with a fluorinating agent provides a corresponding compound of the Formula I in moderate yields.
by weight, more
It has been unexpectedly found that the fluorination process of the present invention can provide compounds of the Formula I in high regioselective and chemical yield containing less than about v 10°/o^3y_.weight> preferablyjes^ than ffkpfo 5%
, and most preferably no
\ preferably less than about 2% by weight, detectable amount, of undesired regioisomers.
In one embodiment, the invention provides a process for the preparation of a compound of the Formula I
A
O
NTR'

R
Formula I wherein:
X is hydrogen, halogen, Ci-C6-alkyl, Ci-C6-haloalkyl, or nitro; and R and R' are independently hydrogen, halo, Ci-C6-alkyl, C2-C6-
alkenyl, C3-Cs-alkynyl, Ci-C6-haloalkyl, C2-C6-haloalkenyl, C2-C7-acyl, C2-C6-alkoxyalkyl, C2-C6-cyanoalkyl, Ci-C3-alkylsulfmyl, Ci-C3-alkylsulfonyl, or Ci-C3-alkylthio-Ci-C3-alkyl;
-4-

the process comprising the step of treating a compound of the Formula II

A...,

Formula II
with a fluorinating agent at a temperature of about 60° jto_about
120° C in the presence of an organic solvent to form a compound of
the Formula I; wherein:
X and R are as defined above;
R' is independently an alkali metal cation, hydrogen, halo, C1-C6-alkyl, C.2-C6-alkenyl, C3-C5-alkynyl, Ci-Ce-haloalkyl, C2-C6-haioalkenyl, C2-C7-acyl, C2-C6-alkoxyalkyl, C2-C6-cyanoalkyl, Ci-C3-alkylsulfinyl, Ci-C3-alkylsulfonyl, or Ci-C3-alkylthio-Ci-C3-alkyl; and
X, R or R' can optionally be independently protected with a protecting
group which is substantially stable to the fluorinating agent.
In another embodiment, R and R' are independently hydrogen,
halo, Ci-Ce-alkyl, C2-C6-alkyl, Ci-Ce-haloalkyl, C2-C6-haloalkyl or C2-
C7-acyl.
In yet another embodiment, X is H or halogen; R is Ci-C6-alkyl;
and R' is Ci-C6-haloalkyl. In still yet another embodiment, X is
chloro; R is methyl; and R' is difluoromethyl.
ENTAILED DESCRIPTION OF THE INVENTION
The yields of the present process depend, among other things, upon the temperature at which the treatment is conducted, the mode, rate or order of addition into a reaction vessel of the
-5-


fluorinating agent and the compound of the Formula II, the molar ratio of the fluorinating agent to the compound of the Formula II, or the solvent employed or a catalyst employed.
The process of the present invention can be run at temperatures ranging from about 60° C to a temperature which is at or below the boiling point of the organic solvent(s) used. The optimal temperature for running the fluorination reaction will depend, among other things, upon the organic solvent or combination of organic solvents used to run the reaction. The optimal temperature will generally range from about 60° to about 120° C, preferably from about 80° to about 115° C, more preferably from about 80° to about 85° C.
The modifier "about" is usedherein to indicate tha|_certain
preferred operating ranges, such as material amounts and temperature, and ranges thereof, are not fixedly determined• JTfre meaning will often be apparent to one of ordinary skill. For example, a recitation of a temperature range of about 60° C to about 120° C in reference to, for example, the aforementioned fluorination reaction would be interpreted to include other like temperatures which can be expected to favor a useful rate of reaction, such as, for example, 54° C or 132° C. Where guidance from the experience of those of ordinary skill is lacking, guidance from the context is lacking, and where a more specific rule is not recited below, the "about" range shall be not more than 10% of the absolute value of an end point or 15% of the range recited, whichever is less.


Fluorinating agents that may be used in accordance with the present invention are electrophilic NF reagents and xenon difluoride. NF reagents are electrophilic fluorinating agents that contain a fluorine atom bound to a nitrogen atom which is part of an organic compound. NF reagents serve as F4 transfer agents.^a€^F fluorinating reagents used in the present invention can include those described by LaTet al. {Chem. Rev., 1996, 96, 1737^1.755), Lai (J. Org. Chem, 1993, 58, 2791-2796), and Banks et al. (J. Chem. Soc, Chem. Commun. 1992, 595-596), the relevant disclosures of which are hereby incorporated by reference. Examples of electrophilic NF reagents include but are not limited to fluorine triethylenediamine (F-TEDA), N-fluoro-o^b^nzenesulfonimi.de,^and N-fluoro-2-pyridone.
/


The electrophilic NF reagent can include any of the following:




(A")2
R= silyl, -CH2C1 A= BF4, OTf

CF3S02—NF


N


Tf







(CF3S02)2NF

SOf^

Sx^so',

In a particular embodiment, the fluorinating agent is fluorine triethylenediamine.
The fluorinating agent can be added to the fluorination reaction mixture in a single portion, in at least two portions, or continuously as either a solid or solution containing the fluorinating agent. For example, the fluorinating agent can be added as a powdered solid in two or more portions, or it can be added continuously to the fluorination reaction, as a solution or suspension comprising an organic solvent and the fluorinating agent, by way of a syringe, peristaltic or metering pump. The amount, in terms of
-8-

molar equivalents, of fluorinating agent in each aliquot or portion can be varied as desired.
The process of the invention can be run at ambient to elevated pressure or generally from about atmospheric pressure or 1 atmosphere to about 10 atmospheres. The fluorination reaction can be accelerated by increasing the pressure under which the reaction is run.
The process of the invention is run for a period of time sufficient to form the compound of the ForrnulajT-^Fhe-fl«©i4na4aon reaction time preferably ranges from about 4 to about 72 hours for completion, more preferably from about 6 to about 48 hours, and can vary according to the reaction temperature, the solvent employed, the presence or absence of a catalyst, the structure of the compound of the Formula I, the fluorinating agent employed and other factors. For example, the fluorination reaction is generally faster when R' is hydrogen than when R' is difluoromethyl.
The concentration of a compound of the Formula II in the reaction solvent can range from about 5 % to about 25%. preferably from about 10% to about 25%, more preferably from about 15% to about 20% by weight, based upon the final weight of the reaction mixture. Generally, about 5 to about 50, preferably about 10 to about 30, volumes mL or L of solvent per g or Kg, respectively, of the compound of the Formula II are used.
The compound of the Formula I can be isolated from the reaction mixture and purified according to the methods disclosed in Example 1 or according to other methods known to those of skill in the art. For example, the solvent can be evaporated or otherwise removed from the reaction mixture to form a residue, and the


compound of the Formula I can be isolated from the resulting residue by vacuum distillation or sublimation.
A wide range of organic solvents can be employed in the presently claimed process. The organic solvent will generally be able to dissolve at least a portion of either one or both of the compound of the Formula I and the fluorinating agent. The organic solvents that may be useful in the present invention include, but are not limited to, acetonitrile, xylene, nitrobenzene, ethyl acetate, dichloromethane, N,N-dimethylformamide (DMF), tetrahydrofuran (THF), aqueous solutions of the above solvents which are water-miscible, and combinations thereof. In one embodiment, the organic solvent is acetonitrile.
Smtablef halogenated solvents include: carbon tetrachloride, bromodiehloromethane, dibromochloromethane, bromoform, chloroform, bromochloromethane, dibromomethane, butyl chloride, dichloromethane, tetrachloroethylene, trichloroethylene, 1,1,1-trichloroethane, 1,1,2-trichloroethane, 1,1-dichloroethane, 2-chloropropane, hexafluorobenzene, 1,2,4-trichlorobenzene, and o-dichlorobenzene.
Suitable ether solvents include: dimethoxymethane, tetrahydrofuran, 1,3-dioxane, 1,4-dioxane, furan, diethyl ether, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, triethylene glycol dimethyl ether, t-butyl ethyl ether, and t-butyl methyl ether.
Suitable protic solvents may include, by way of example and without limitation, water, ethylene glycol, diethylene glycol, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, anisole, and glycerol.
10


Suitable aprotic solvents may include, by way of example and without limitation, dimethylformamide (DMF), dimethylacetamide (DMAC), 1,3-dimethyl-3,4,5,6-tetrahydro-2(lH)-pyrimidinone (DMPU), formamide, ethyl formate, l,3-dimethyl-2-imidazolidinone (DMI), N-methylpyrrolidinone (NMP), N-methylacetamide, N-methylformamide, acetonitrile, dimethyl sulfoxide, propionitrile, methyl acetate, ethyl methyl ketone, ethyl acetate, sulfolane, N,N-dimethylpropionamide, tetramethylurea, nitrobenzene, and hexamethylphosphoramide.
Suitable acidic solvents include, by way of example and without limitation, trifiuoroacetic acid and acetic acid.
Suitable hydrocarbon solvents include, by way of example and without limitation, cyclohexane, pentane, hexane, cycloheptane, methylcyciohexane, heptane, octane, indane, and nonane.
The present process can be run in the solution phase or in a biphasic, i.e., solid/liquid or liquid/liquid, reaction system. When a biphasic reaction system is employed, a phase transfer catalyst can be used to aid in the dissolution of the either one or both the fluorinating agent and the compound of the Formula II in the liquid phase. Such phase transfer catalysts include those disclosed in Starks et al., "Phase-Transfer Catalysis: Fundamentals, Applications, and Industrial Perspectives" (Chapman 85 Hall, NY; 1994), the disclosure of which is hereby incorporated by reference.
Generally, the fluorination of a compound of the Formula II in a suitable solvent, such as those recited hereinabove, and most preferably acetonitrile, with at least two aliquots each of about 0.8 to about 1.6, preferably about one, molar equivalent of a fluorinating agent provides yields of about 50% to about 70% of theoretical yield of a compound of the Formula I within from about 4 to about 72
11

\f>-
hours, preferably about 6 to about 48 hours from the onset of reaction.


When necessary, the groups X, R and/or R' can be independently protected witha^suitable protecting group which is substantially stable to the fluorinating agent and/or the reaction conditions of the fluorination process of the present.invention. As used herein, the term^protecting group referstoany of a number of chemical protecting groups known to those_of ordinary, skillin the \ art, which groups are used to protect.radicals or^substituents, such \ as X, R and/or R', from degradation by ja^fluorinating agent .and/or \ reaction conditions of fluorination. Such groups include, but are not limited to those disclosed in Greene and Wuts, "ProtectivejGroups in Organic Synthesis" (John Wiley & Sons NY; 1991);» the relevant disclosure of which is hereby incorporated by reference.
'As used herein and unless otherwise indicated, the term "alkyl", when used alone or as part of a larger moiety, includes one to six, preferably one to four, carbon atoms. As used herein and unless otherwise indicated, the term "alkenyl", when used alone or as part of a larger moiety, includes two to six, preferably two to four, carbon atoms. The terms alkyl and alkenyl should be understood to include the straight chain, branched and cyclic forms of those groups.
As used herein and unless otherwise indicated, the terms "haloalklyl" and "haloalkenyl" refer to alkyl or alkenyl groups, respectively, as defined above which are substituted by one or more halogens. Such haloalkyl groups include, but are not limited to, fluoromethyl, difluoromethyl, trifluoromethyl, difluorochloromethyl, fluoropropyl, and difluoroethyl. Such haloalkenyl groups include, but are not limited to, fluoroethylenyl, bromopropylenyl,




bromoethylenyl, dichloroethylenyl, dibromoethylenyl, bromobutanyl, chlorobutenyl, and dibromobutenyl.
As used herein and unless otherwise indicated, the term acyl refers to a substituent having a carbonyl group attached to a C1-C6 alkyl or a C2-C6 alkenyl, wherein the carbonyl group is attached to the triazolinone ring.
As useoUiereiiiand unless otherwise indicated, the terms "halogen" or "halo" refers to fluorine, bromine, chlorine, or iodine.
It will be appreciated that certain compounds of the present invention can contain an asymmetrically substituted carbon atom, and may be isolated in optically active or racemic forms. It is well known in the art how to prepare optically active forms, such as by resolution of racemic forms or by synthesis, from optically active starting materials. Many geometric isomers of olefins and the like can also be present in the compounds described herein, and all such stable isomers are contemplated in the present invention. Also, it is realized that cis and trans geometric isomers of the compounds of the present invention are described and may be isolated as a mixture of isomers or as separated isomeric forms. All chiral, diastereomeric, and racemic forms of the compounds of the Formulae I and II are included in the present invention.
Combinations of substituents and/or variables are permissible only if such-combinations result in stable compounds. By stable compound or stable structure it is meant herein a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture.
The term "substituted", as used herein, means that any one or more hydrogens on the designated atom is replaced with a selection from the indicated group, provided that the designated atom's


PCT/US99/1
normal valency is not exceeded, and that the substitution results in a stable compound.
v2he'~compound of the Formula II was prepared according to Example 2 below and according to the procedures described in United States Patents 4,980,480 and 5,468,868, the disclosures of which are hereby incorporated by reference. Unless otherwise noted, all other materials used herein are commercially available from sources such as Aldrich Chemical Co., Inc., Aceto Corporation, Acros Organics, Air Products, Apollo Scientific, Ltd., Albright 8s Wilson Americas, Bachem, AlliedSignal Corporation, BASF Aktiengesellschaft, Borregaard Fine Chemicals, Bridgewater Chemical, BNFL Fluorochemicals Ltd., Eastman Chemical Company, Elan Incorporated, Fluorochem Ltd., Fluka Chemie AG, Fisher Scientific, INDOFINE Chemical Company, Inc., JRD Fluorochemicals Ltd., Kanto Chemicals Co., Inc., Lancaster Synthesis Ltd., Research Organics Inc., Strem Chemicals, Inc., Wychem Ltd., or VWR Scientific.
The foregoing will be better understood with reference to the follewing examples which detail certain procedures for the manufacture of triazolinones according to the present invention. All references made to these examples are for the purposes of illustration. They are not to be considered limiting as to the scope and nature of the present invention because further modifications of the disclosed invention will be apparent to those skilled in the art. All such modifications are deemed to be within the scope of the present invention.
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Example 1
Preparation of the Compound of the Formula I: 4,5-Dihydro-1 -(4-chloro-2-fluorc)ph^n-\dj^^me&ylr4jidifluoromethvl-
1,2,4-triaz0l-S(-l-H)-one-
Under a nitrogen atmosphere, a stirred solution of 5.0 grams (0.0192 mole -1.0 equiv.) of 4,5-Dihydro-l-(4-chlorophenyl)-3-methyl-4-difluoromethyl-1,2,4-triazol-5(lMJjone_and6:8 grams (0.0192 mole - 1.0 equiv.) of F-TEDA in _50 mL of acetonitrile (%Wt/Vol triazolinone to solvent - 10%) was stirred at 82° C for 24 hours. After this time, an additional 6.8 grams (0.0192 mole - 1.0 equiv.) of F-TEDA was added. Upon completion of addition, the reaction mixture was stirred at 82° C for an additional 24 hours. The reaction mixture was analyzed by gas chromatography (GC), which indicated the reaction was 78% complete. The reaction
mixture was cooled to ambient temperature, and the acetonitrile was
- — "■—~——~~—— ■ f
removed under reduced pressure. The resulting residue was taken up in 30 mL of water and then 40 mL of an aqueous 10% hydrochloric acid solution was added. The resulting solution was extracted with three 30 mL portions of ethyl acetate. The organic layer was separated from the aqueous layer, dried with magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure, yielding 2.9 grams (48% yield) of titlej^mpound. ThfixH1 NMR spectrum of the product was consistent with that of a reference sample.
15


Example 2
Preparation of the compound of the Formula II:
4,S-dihydro-3-methyl-l-(4-chlorophenyl)-l,2,4-triazol-5(lH)-one and
4,5-dihydro-3-methyl-l-phenyl-l,2,4-triazol-5(lH)-one
The following procedure is described in U.S. Patent No. 4,980,480.
Chlorine gas was bubbled into a solution of 17.7 g (0.1 mol) of 3-methyl-l-phenyl-1,2,4-triazolidin-5-one in.about 10 times its weight of glacial acetic acid at room temperature for 5 minutes. The temperature rose to 35° C, and the brown solution became lighter in cofor. WMR analysis showed that the product was 4,5-di'hydro-3-methyl-l-phenyl-l,2,4-triazol-5(lH)one. Next 1.0 g of iron powder was slowly added to the mixture which was then heated to 95° C. Chlorine gas was bubbled into it for 10 minutes, after which it was maintained at the elevated temperature for one hour while stirring. The mixture was then dumped into ice, extracted with ethyl acetate, dried over magnesium sulfate and passed through a column of silica gel (which was then eluted with 200 ml of ethyl acetate to give a solution from which the solvent was then evaporated under reduced pressure), giving 12.0 g of a solid (m.p. 174°-176° C), 4,5-dihydro-3-methyl-i-(4-chlorophenyl)-l,2,4-triazol-5(lH)-one. The H1 NMR spectrum of the product was consistent with that of a reference sarnple.
The above is a detailed description of particular embodiments of the invention. It is recognized that departures from the disclosed embodiments may be made within the scope of the invention and that obvious modifications will occur to a person skilled in the art. Those of skill in the art should, in light of the present disclosure, appreciate


that many changes can be made in the specific embodiments which are disclosed herein and still obtain a like or similar result without departing from the spirit and scope of the invention. All of the embodiments disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. /



WE CLAIM:
1. A process for the preparation of a 3, 4-disubstituted -l-(4-substituted-2-fluorophenyl-l,2,4-triazolin-5-one compound of the Formula I

wherein:
X is hydrogen, halogen, Ci-C6-alkyl, Ci-C6-haloalkyl, or nitro; and
R and R* are independently hydrogen, halo, Ci-C6-alkyl, C2-C6-alkenyl, C3-
Cs.-alkynyl, Ci-C6-haloalkyl, C2-C6-haloalkenyl, C2-C7-acyl, C2-C6-
alkoxyalkyl, C2-C6-cyanoalkyl, Ci-C3-alkylsulfinyl, Ci-C3-alkylsulfonyl, or
Ci-Cs-alkylthio-Ci-Cs-alkyl;
the process comprising the step of treating a compound of the Formula II

with a fluorinating agent at a temperature of from 60° to 120°C in the
presence of an organic solvent to form a compound of the Formula I;
wherein:
X and R are as defined above: and
R' is independently an alkali metal cation, hydrogen, halo, Ci-C6-alkyl, C2-
Ce-alkenyl, C3-Cs-alkynyl, Ci-Ce-haloalkyl, C2-C6- haloalkenyl, C2-C7-acyl,
C2-C6-alkoxyalkyl, C2-C6-cyanoalkyl, Ci-C3-alkylsulfmyl, Ci-C3-alkylsulfonyl,
or Ci-Cs-alkylthio^Ci^C^alkyl.
-18-

The process as claimed in claim 1, wherein X, R or R' are independently protected with a protecting group that is substantially stable to the fluorinating agent.
The process as claimed in claim 1, wherein X is halogen; R is C1-C6-alkyl; and R' is Ci-C6-haloalkyl.
The process as claimed in claim 1, wherein X is chloro; R is methyl; and R' is difluoromethyl.
The process as claimed in claim 1, wherein the fluorinating agent is an electrophilic NF reagent.
The process as claimed in claim 1, wherein the electrophilic NF reagent is fluoro triethylenediamine.
The process as claimed in claim 1, wherein R and R' are independently hydrogen, halo, Ci-C6-alkyl, C2-C6-alkyl, Ci-C6-haloalkyl, C2-C6-haloalkyl or C2-C7-acyl.
The process as claimed in claim 1, wherein the organic solvent is acetonitrile, xylene, nitrobenzene, ethyl acetate, dichloromethane, N,N-dimethylformamide, tetrahydrofuran, or an aqueous mixture containing one or more of said organic solvents.
The process as claimed in claim 1, wherein the organic solvent is acetonitrile.
-19-

10. The process as claimed in claim 1, wherein the compound of the Formula II is treated with the fluorinating agent at a temperature of 60° to 100°C for a period of from about 4 to about 72 hours.
11. The process as claimed in claim 1, wherein the compound of the Formula II in acetonitrile is treated with the fluorinating agent at a temperature of from 80° to 85°C for a period of from about 6 to 48 hours.
12. The process as claimed in claim 1, wherein the compound of the
r
Formula II is treated with at least two separate aliquots of from about 0.8 to about 1.6 molar equivalents each of fluorinating agent per mole of compound of the Formula II.
13. The process as claimed in claim 1, wherein X is chloro, R is methyl, R' is difluoromethyl, the fluorinating agent is an electrophilic NF reagent, and the organic solvent is acetonitrile.
14. The process as claimed in claim 1, wherein the alkali metal cation is Li+Na+ or K+.
Dated this 19th day of February, 2001
[JAfiTANTA PAL]
OF REMERY & SAGAR
ATTORNEY FOR THE^APPLICANTS
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Documents:

in-pct-2001-00179-mum-cancelled pages(22-3-2005).pdf

in-pct-2001-00179-mum-claims(granted)-(22-03-2005).doc

in-pct-2001-00179-mum-claims(granted)-(22-3-2005).pdf

in-pct-2001-00179-mum-correspondence(27-2-2007).pdf

in-pct-2001-00179-mum-correspondence(ipo)-(13-10-2006).pdf

in-pct-2001-00179-mum-form 1(17-2-2001).pdf

in-pct-2001-00179-mum-form 19(16-4-2004).pdf

in-pct-2001-00179-mum-form 2(granted)-(22-03-2005).doc

in-pct-2001-00179-mum-form 2(granted)-(22-3-2005).pdf

in-pct-2001-00179-mum-form 3(19-2-2001).pdf

in-pct-2001-00179-mum-form 3(22-3-2005).pdf

in-pct-2001-00179-mum-form 5(19-2-2001).pdf

in-pct-2001-00179-mum-form-pct-isa-210(19-2-2001).pdf

in-pct-2001-00179-mum-other documents(22-3-2004).pdf

in-pct-2001-00179-mum-petition under rule 137(22-3-2005).pdf

in-pct-2001-00179-mum-petition under rule 138(22-3-2005).pdf

in-pct-2001-00179-mum-power of authority(13-4-2001).pdf

in-pct-2001-00179-mum-power of authority(22-3-2005).pdf


Patent Number 204554
Indian Patent Application Number IN/PCT/2001/00179/MUM
PG Journal Number 24/2007
Publication Date 15-Jun-2007
Grant Date 27-Feb-2007
Date of Filing 19-Feb-2001
Name of Patentee FMC CORPORATION
Applicant Address 1735 MARKET STREET, PHILADELPHIA, PENNSYLVANIA, 19103, UNITED STATES OF AMERICA,
Inventors:
# Inventor's Name Inventor's Address
1 JAIDEV GOUDAR 25-08 FOX RUN DRIVE, PLAINSBORO, NJ 08536, USA
PCT International Classification Number C 07 D 249/12
PCT International Application Number PCT/US99/19787
PCT International Filing date 1999-08-27
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 60 / 098,060 1998-08-27 U.S.A.