Title of Invention	A NOVEL METHOD FOR PREPARATION OF CARBAMIC ACID- (CHLOROCARBONYL)-[(4-TRIFLUOROMETHOXY) PHENYL] METHYL ESTER
Abstract	Carbamic Acid- (chlorocarbonyl)-[(4-Trifluoromethoxy) phenyl] methyl ester compound (I) is prepared reaction of p-Trifluoromethoxy aniline carbate compound with Triphosgene (CI₃OC₃OOCI₃) or Diphosgene (CIC₂OOCI₃) in the presence of aliphatic tertiary amines with C₁-C4 alkyl like triethyl amine, tributyl amine tri isopropyl amine or aromatic amine like pyridine picolines, N.N-Dimethyl aniline using aniline using aromatic hydrocarbon like chlorobenzene, dichloro benzene, toluene or xylene as a solvent at -10ºC to 50ºC

Title of Invention

A NOVEL METHOD FOR PREPARATION OF CARBAMIC ACID- (CHLOROCARBONYL)-[(4-TRIFLUOROMETHOXY) PHENYL] METHYL ESTER

Abstract

Carbamic Acid- (chlorocarbonyl)-[(4-Trifluoromethoxy) phenyl] methyl ester compound (I) is prepared reaction of p-Trifluoromethoxy aniline carbate compound with Triphosgene (CI₃OC₃OOCI₃) or Diphosgene (CIC₂OOCI₃) in the presence of aliphatic tertiary amines with C₁-C4 alkyl like triethyl amine, tributyl amine tri isopropyl amine or aromatic amine like pyridine picolines, N.N-Dimethyl aniline using aniline using aromatic hydrocarbon like chlorobenzene, dichloro benzene, toluene or xylene as a solvent at -10ºC to 50ºC

Full Text	FORM 2 The Patent Act 1970, (39 of 1970) & The Patent rule 2003 Complete Specification (See Section 10 and Rule 13) 1. TITLE OF THE INVENTION "A novel method for preparation of Carbamic Acid-(chlorocarbonyl)-[(4-Trifluoromethoxy) phenyl] methyl ester" 2. APPLICANTS) (a) NAME : GHARDA CHEMICALS LTD (b) NATIONALITY: INDIAN (c) ADDRESS: B-27/29, MIDC, PHASE 1, DOMBIVLI. DIST. THANE, PIN 421 203 MAHARASHTRA INDIA 3. PREAMBLE OF THE DESCRIPTION The following specification particularly describes the invention and the manner in which it is to be performed. TITLE A novel method for preparation of Carbamic Acid-(chlorocarbonyl)-[(4-Trifluoromethoxy) phenyl] methyl ester (I) BACKGROUND OF INVENTION The present invention pertains to the preparation of Carbamic Acid-(chlorocarbonyl)-[(4-Trifluoromethoxy) phenyl] methyl ester (I) which is an intermediate in the preparation of an arthropodicidal oxadiazine e.g. (II) Oxadiazines such as those disclosed in WO 9211249 and WO 9319045 are important arthropodicidal compounds and effective preparative methods are needed. Compound (I) is used for the preparation of compound (II), which is a particularly advantageous arthropodicidal Oxadiazine c=o \\ // OCR COOCH3 (II) Preparation of compound (I) is reported in literature by reacting p-Thfluoromethoxy aniline carbamate [Compound (III)] with Phosgene in presence of base. 1 US patent 5510505 discloses a preparation of compound (I) by treating compound (III) with a base such as sodium hydride or sodium methoxide and the solvent like benzene, toluene and then treating with an excess of Phosgene at -10 to 100°C. Drawback of this procedure is handing of sodium hydride, which is not only a hazardous compound but causes fire when exposed to atmosphere. Phosgene is a highly toxic compound and requires very special operating conditions. Present invention overcomes all these problems by avoiding use of either Sodium hydride/Sodium methoxide or Phosgene.The present invention permits use of trialkyl amines and Triphosgene/Diphosgene as a phosgene source which is comparatively safe for handling. SUMMARY OF INVENTION According to present invention, compound (I) is prepared by reaction of compound (III) with Triphosgene (CI3OC3OOCI3) or Diphosgene (CIC2OOCI3) instead of phosgene gas in the presence of aliphatic tertiary amines with C1-C4 alkyl or aromatic amines like pyridine, picolines, N,N-Dimethyl aniline as bases using aromatic hydrocarbon like chlorobenzene, toluene or xylene as a solvent at -10CC to 50°C. Handling of Triphosgene or Diphosgene is safe as compared to Phosgene gas. DETAILS OF INVENTION The compound of formula (I) can be prepared by the process of this invention which comprises the process variations as describe below. The phosgene source is used in the process is Diphosgene (CIC2OOCI3) or Triphosgene (CI3OC3OOCI3), preferably Triphosgene The amount of Diphosgene/Triphosgene can be 3-5 moles per mole of p-Trifluoromethoxy Aniline carbamate (III), preferably 2.5 - 4 moles per mole. The solvent used in the process of this invention can be any non reactive hydrocarbon aromatic solvent. Most preferred are toluene, xylene, chlorobenzene, dichlorobenzene. The quantity of solvent used for reaction is 500 ml to 3000 ml. per mole of p-Trifluoromethoxy Aniline Carbamate(lll), preferably 1000 ml. per mole. The base used for reaction is aliphatic tertiary amines with C1-C4 alkyl groups like Triethyl amine, Tributyl amine. Tri-isopropylamine or aromatic amines like pyridine, picolines, N.N-Dimethyl aniline, preferably Triethyl amine or Pyridine 2 Quantity of base is used is 1-5 moles of base per mole of p-Trifluoromethoxy Aniline Carbamate (III) preferably 1-2 moles per mole. The reaction is carried out at -10°C to 50°C at ambient pressure, preferably at a temperature between -10°C and 25°C, more preferably between -5°Cand15°C. The process accordingly to the invention can be carried out batch wise. A solution of Triphosgene in solvent is added into mixture of p-Trifluoromethoxy Aniline and base in solvent at -10°C. Temperature of reaction mass raised to ambient temperature and stirred. The final product Carbamic Acid-(chlorocarbonyl) - [(4-Trifluoromethoxy) phenyl] methyl ester (I) is isolated by drowning in 2 N HCI soln. followed by layer separation, concentration and crystallization with hexane. The examples which follow are given by way of indication in order to illustrate the invention. EXAMPLE-1 To a solution of 117.5 gm of Trifluoro methoxy aniline carbamate and 1000 ml. toluene, add 51 gm. of Triethyl amine and stir to get a clear solution. Prepare a clear solution of 149 gm triphosgene into 500 ml. of toluene. Add Triphosgene solution in toluene into a mixture of Trifluoro methoxy aniline carbamate and Triethyl amine at 0°C over a period of 4 hr. Raise temperature of mass to 30°C & stir for 4 hrs. Product Carbamic Acid-(chlorocarbonyl) - [(4-Trifluoromethoxy) phenyl] methyl ester isolated by drowning in 2 N HCI soln. followed by layer separation, concentration and crystallization by hexane. 155 gm. of product obtained with 97% GC purity. EXAMPLE-2 To a solution of 117.5 gm of Trifluoro methoxy aniline carbamate and 750 ml toluene, add 79 gm. of Pyridine and stir to get a clear solution. Prepare a clear solution of 149 gm triphosgene into 350 ml. of toluene. Add Triphosgene solution in toluene into a mixture of Trifluoro methoxy aniline carbamate and Pyridine at -5°C over a period of 3 hr. Raise temperature of mass to 30°C & stir for 4 hrs. Product Carbamic Acid-(chlorocarbonyl) - [(4-Trifluoromethoxy) phenyl] methyl ester isolated by drowning in 2 N HCI soln. followed by layer separation, concentration and crystallization by hexane. 145 gm. of product obtained with 96.5% GC purity. 3 EXAMPLE-3 To a solution of 117.5 gm of Trifluoro methoxy aniline carbamate and 1000 ml toluene, add 173 gm. of Tri-n-butyl amine and stir to get a clear solution. Prepare a clear solution of 149 gm triphosgene into 500 ml. of toluene. Add Triphosgene solution in toluene into a mixture of Trifluoro methoxy aniline carbamate and Tri n-butyl amine amine at -5°C over a period of 4 hr. Raise temperature of mass to 30°C & stir for 4 hrs. Product Carbamic Acid-(chlorocarbonyl) - [(4-Trifluoromethoxy) phenyl] methyl ester isolated by drowning in 2 N HCI soln. followed by layer separation, concentration and crystallization by hexane. 150 gm. of product obtained with 97% GC purity. EXAMPLE- 4 To a solution of 117.5 gm of Trifluoro methoxy aniline carbamate and 1000 ml. o-xylene, add 51 gm. of Triethyl amine and stir to get a clear solution. Prepare a clear solution of 100 gm diphosgene into 500 ml. of o-xylene. Add Diphosgene solution in o-Xylene into a mixture of Trifluoro methoxy aniline carbamate and Triethyl amine at 0°C over a period of 4 hr. Raise temperature of mass to 30°C & stir for 4 hrs. Product Carbamic Acid-(chlorocarbonyl) - [(4-Trifluoromethoxy) phenyl] methyl ester isolated by drowning in 2 N HCI soln. followed by layer separation, concentration and crystallization by hexane. 155 gm. of product obtained with 97% GC purity. 4 WE CLAIM 1. Carbamic Acid-(chlorocarbonyl)-[(4-Trifluoromethoxy) phenyl] methyl ester compound (I) is prepared by reaction of p-Trifluoromethoxy aniline Carbate compound (III) with Triphosgene (CI3OC3OOCI3) or Diphosgene (CIC2OOCI3) in the presence of aliphatic tertiary amines with CTC4 alkyl or aromatic amines as a base using aromatic hydrocarbon like chlorobenzene, dichloro benzene, toluene or xylene as a solvent at-10°C to 50°C 2. A process as claimed in claim 1 wherein the condensation is carried out at a temperature of from -10°C to 50°C. 3. A process as claimed in claim 1, wherein the base used is aliphatic tertiary amines with C1-C4 alkyl groups like Triethyl amine, Tributyl amine. Tri isopropyl amine, or aromatic amines like pyridine, picolines, N,N-Dimethyl aniline, preferably Triethyl amine or Pyridine. 4. A process as claimed in claim 1, wherein the solvent used in the process of this invention can be any non reactive hydrocarbon aromatic solvent. like toluene, xylenes, chlorobenzene, dichlorobenzene. Date 13TH Dec. 2005 5 ABSTRACT Carbamic Acid-(chlorocarbonyl)-[(4-Trifluoromethoxy) phenyl] methyl ester compound (I) is prepared by reaction of p-Trifluoromethoxy aniline carbate compound with Triphosgene (CI3OC3OOCI3) or Diphosgene (CIC2OOCI3) in the presence of aliphatic tertiary amines with CrC4 alkyl like triethyl amine, tributyl amine, tri isopropyl amine or aromatic amines like pyridine, picolines, N,N-Dimethyl aniline using aromatic hydrocarbon like chlorobenzene, dichloro benzene, toluene or xylene as a solvent at -10°C to 50°C 6

Full Text

FORM 2
The Patent Act 1970,
(39 of 1970)
&
The Patent rule 2003
Complete Specification
(See Section 10 and Rule 13)
1. TITLE OF THE INVENTION
"A novel method for preparation of Carbamic Acid-(chlorocarbonyl)-[(4-Trifluoromethoxy) phenyl] methyl ester"
2. APPLICANTS)
(a) NAME : GHARDA CHEMICALS LTD
(b) NATIONALITY: INDIAN
(c) ADDRESS: B-27/29, MIDC, PHASE 1, DOMBIVLI.
DIST. THANE, PIN 421 203 MAHARASHTRA INDIA
3. PREAMBLE OF THE DESCRIPTION
The following specification particularly describes the invention and the manner in which it is to be performed.

TITLE
A novel method for preparation of Carbamic Acid-(chlorocarbonyl)-[(4-Trifluoromethoxy) phenyl] methyl ester (I)

BACKGROUND OF INVENTION
The present invention pertains to the preparation of Carbamic Acid-(chlorocarbonyl)-[(4-Trifluoromethoxy) phenyl] methyl ester (I) which is an intermediate in the preparation of an arthropodicidal oxadiazine e.g. (II)
Oxadiazines such as those disclosed in WO 9211249 and WO 9319045 are important arthropodicidal compounds and effective preparative methods are needed.
Compound (I) is used for the preparation of compound (II), which is a particularly advantageous arthropodicidal Oxadiazine

c=o

\\ //
OCR

COOCH3
(II)
Preparation of compound (I) is reported in literature by reacting p-Thfluoromethoxy aniline carbamate [Compound (III)] with Phosgene in presence of base.

1

US patent 5510505 discloses a preparation of compound (I) by treating compound (III) with a base such as sodium hydride or sodium methoxide and the solvent like benzene, toluene and then treating with an excess of Phosgene at -10 to 100°C. Drawback of this procedure is handing of sodium hydride, which is not only a hazardous compound but causes fire when exposed to atmosphere. Phosgene is a highly toxic compound and requires very special operating conditions.
Present invention overcomes all these problems by avoiding use of either Sodium hydride/Sodium methoxide or Phosgene.The present invention permits use of trialkyl amines and Triphosgene/Diphosgene as a phosgene source which is comparatively safe for handling.
SUMMARY OF INVENTION
According to present invention, compound (I) is prepared by reaction of compound (III) with Triphosgene (CI3OC3OOCI3) or Diphosgene (CIC2OOCI3) instead of phosgene gas in the presence of aliphatic tertiary amines with C1-C4 alkyl or aromatic amines like pyridine, picolines, N,N-Dimethyl aniline as bases using aromatic hydrocarbon like chlorobenzene, toluene or xylene as a solvent at -10CC to 50°C. Handling of Triphosgene or Diphosgene is safe as compared to Phosgene gas.
DETAILS OF INVENTION
The compound of formula (I) can be prepared by the process of this invention which comprises the process variations as describe below.
The phosgene source is used in the process is Diphosgene (CIC2OOCI3) or Triphosgene (CI3OC3OOCI3), preferably Triphosgene
The amount of Diphosgene/Triphosgene can be 3-5 moles per mole of p-Trifluoromethoxy Aniline carbamate (III), preferably 2.5 - 4 moles per mole.
The solvent used in the process of this invention can be any non reactive hydrocarbon aromatic solvent. Most preferred are toluene, xylene, chlorobenzene, dichlorobenzene.
The quantity of solvent used for reaction is 500 ml to 3000 ml. per mole of p-Trifluoromethoxy Aniline Carbamate(lll), preferably 1000 ml. per mole.
The base used for reaction is aliphatic tertiary amines with C1-C4 alkyl groups like Triethyl amine, Tributyl amine. Tri-isopropylamine or aromatic amines like pyridine, picolines, N.N-Dimethyl aniline, preferably Triethyl amine or Pyridine
2

Quantity of base is used is 1-5 moles of base per mole of p-Trifluoromethoxy Aniline Carbamate (III) preferably 1-2 moles per mole.
The reaction is carried out at -10°C to 50°C at ambient pressure, preferably at a temperature between -10°C and 25°C, more preferably between -5°Cand15°C.
The process accordingly to the invention can be carried out batch wise. A solution of Triphosgene in solvent is added into mixture of p-Trifluoromethoxy Aniline and base in solvent at -10°C. Temperature of reaction mass raised to ambient temperature and stirred. The final product Carbamic Acid-(chlorocarbonyl) - [(4-Trifluoromethoxy) phenyl] methyl ester (I) is isolated by drowning in 2 N HCI soln. followed by layer separation, concentration and crystallization with hexane.
The examples which follow are given by way of indication in order to illustrate the invention.
EXAMPLE-1
To a solution of 117.5 gm of Trifluoro methoxy aniline carbamate and 1000 ml. toluene, add 51 gm. of Triethyl amine and stir to get a clear solution. Prepare a clear solution of 149 gm triphosgene into 500 ml. of toluene. Add Triphosgene solution in toluene into a mixture of Trifluoro methoxy aniline carbamate and Triethyl amine at 0°C over a period of 4 hr. Raise temperature of mass to 30°C & stir for 4 hrs. Product Carbamic Acid-(chlorocarbonyl) - [(4-Trifluoromethoxy) phenyl] methyl ester isolated by drowning in 2 N HCI soln. followed by layer separation, concentration and crystallization by hexane. 155 gm. of product obtained with 97% GC purity.
EXAMPLE-2
To a solution of 117.5 gm of Trifluoro methoxy aniline carbamate and 750 ml toluene, add 79 gm. of Pyridine and stir to get a clear solution. Prepare a clear solution of 149 gm triphosgene into 350 ml. of toluene. Add Triphosgene solution in toluene into a mixture of Trifluoro methoxy aniline carbamate and Pyridine at -5°C over a period of 3 hr. Raise temperature of mass to 30°C & stir for 4 hrs. Product Carbamic Acid-(chlorocarbonyl) - [(4-Trifluoromethoxy) phenyl] methyl ester isolated by drowning in 2 N HCI soln. followed by layer separation, concentration and crystallization by hexane. 145 gm. of product obtained with 96.5% GC purity.
3

EXAMPLE-3
To a solution of 117.5 gm of Trifluoro methoxy aniline carbamate and 1000 ml toluene, add 173 gm. of Tri-n-butyl amine and stir to get a clear solution. Prepare a clear solution of 149 gm triphosgene into 500 ml. of toluene. Add Triphosgene solution in toluene into a mixture of Trifluoro methoxy aniline carbamate and Tri n-butyl amine amine at -5°C over a period of 4 hr. Raise temperature of mass to 30°C & stir for 4 hrs. Product Carbamic Acid-(chlorocarbonyl) - [(4-Trifluoromethoxy) phenyl] methyl ester isolated by drowning in 2 N HCI soln. followed by layer separation, concentration and crystallization by hexane. 150 gm. of product obtained with 97% GC purity.
EXAMPLE- 4
To a solution of 117.5 gm of Trifluoro methoxy aniline carbamate and 1000 ml. o-xylene, add 51 gm. of Triethyl amine and stir to get a clear solution. Prepare a clear solution of 100 gm diphosgene into 500 ml. of o-xylene. Add Diphosgene solution in o-Xylene into a mixture of Trifluoro methoxy aniline carbamate and Triethyl amine at 0°C over a period of 4 hr. Raise temperature of mass to 30°C & stir for 4 hrs. Product Carbamic Acid-(chlorocarbonyl) - [(4-Trifluoromethoxy) phenyl] methyl ester isolated by drowning in 2 N HCI soln. followed by layer separation, concentration and crystallization by hexane. 155 gm. of product obtained with 97% GC purity.
4

WE CLAIM
1. Carbamic Acid-(chlorocarbonyl)-[(4-Trifluoromethoxy) phenyl] methyl ester compound (I) is prepared by reaction of p-Trifluoromethoxy aniline Carbate compound (III) with Triphosgene (CI3OC3OOCI3) or Diphosgene (CIC2OOCI3) in the presence of aliphatic tertiary amines with CTC4 alkyl or aromatic amines as a base using aromatic hydrocarbon like chlorobenzene, dichloro benzene, toluene or xylene as a solvent at-10°C to 50°C

2. A process as claimed in claim 1 wherein the condensation is carried out at a temperature of from -10°C to 50°C.
3. A process as claimed in claim 1, wherein the base used is aliphatic tertiary amines with C1-C4 alkyl groups like Triethyl amine, Tributyl amine. Tri isopropyl amine, or aromatic amines like pyridine, picolines, N,N-Dimethyl aniline, preferably Triethyl amine or Pyridine.
4. A process as claimed in claim 1, wherein the solvent used in the process of this invention can be any non reactive hydrocarbon aromatic solvent. like toluene, xylenes, chlorobenzene, dichlorobenzene.
Date 13TH Dec. 2005
5

ABSTRACT
Carbamic Acid-(chlorocarbonyl)-[(4-Trifluoromethoxy) phenyl] methyl ester compound (I) is prepared by reaction of p-Trifluoromethoxy aniline carbate compound with Triphosgene (CI3OC3OOCI3) or Diphosgene (CIC2OOCI3) in the presence of aliphatic tertiary amines with CrC4 alkyl like triethyl amine, tributyl amine, tri isopropyl amine or aromatic amines like pyridine, picolines, N,N-Dimethyl aniline using aromatic hydrocarbon like chlorobenzene, dichloro benzene, toluene or xylene as a solvent at -10°C to 50°C

6

Documents:

1543-MUM-2005-ABSTRACT(4-1-2010).pdf

1543-mum-2005-abstract(complete)-(13-12-2005).pdf

1543-mum-2005-abstract(granted)-(11-6-2010).pdf

1543-mum-2005-abstract.doc

1543-mum-2005-abstract.pdf

1543-MUM-2005-CANCELLED PAGES(4-1-2010).pdf

1543-MUM-2005-CLAIMS(AMANDED)-(4-1-2010).pdf

1543-mum-2005-claims(complete)-(13-12-2005).pdf

1543-mum-2005-claims(granted)-(11-6-2010).pdf

1543-mum-2005-claims.doc

1543-mum-2005-claims.pdf

1543-MUM-2005-CORRESPONDENCE(3-6-2009).pdf

1543-MUM-2005-CORRESPONDENCE(7-1-2009).pdf

1543-mum-2005-correspondence(ipo)-(7-7-2010).pdf

1543-mum-2005-description (complete).pdf

1543-mum-2005-description(complete)-(13-12-2005).pdf

1543-mum-2005-description(granted)-(11-6-2010).pdf

1543-mum-2005-form 18(9-10-2007).pdf

1543-mum-2005-form 2(complete)-(13-12-2005).pdf

1543-mum-2005-form 2(granted)-(11-6-2010).pdf

1543-MUM-2005-FORM 2(TITLE PAGE)-(4-1-2010).pdf

1543-mum-2005-form 2(title page)-(complete)-(13-12-2005).pdf

1543-mum-2005-form 2(title page)-(granted)-(11-6-2010).pdf

1543-MUM-2005-FORM 3(3-6-2009).pdf

1543-MUM-2005-FORM 3(4-1-2010).pdf

1543-MUM-2005-FORM 3(7-1-2009).pdf

1543-MUM-2005-FORM 5(3-6-2009).pdf

1543-MUM-2005-FORM 5(4-1-2010).pdf

1543-mum-2005-form-1.pdf

1543-mum-2005-form-2.pdf

1543-mum-2005-form-3.pdf

1543-MUM-2005-REPLY TO EXAMINATION REPORT(4-1-2010).pdf

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Patent Number

240984

Indian Patent Application Number

1543/MUM/2005

PG Journal Number

25/2010

Publication Date

18-Jun-2010

Grant Date

11-Jun-2010

Date of Filing

13-Dec-2005

Name of Patentee

GHARDA CHEMICALS LTD

Applicant Address

B-27/29,MIDC, PHASE 1, DOMBIVLI, DIST. THANE. PIN 421 203,

Inventors:

#	Inventor's Name	Inventor's Address
1	JOSEPH PULINATTU CHERIAN	B-27/29,MIDC, PHASE 1, DOMBIVLI, DIST. THANE. PIN 421 203
2	JAIN NANDKUMAR JANARDAN	B-27/29,MIDC, PHASE 1, DOMBIVLI, DIST. THANE. PIN 421 203
3	MALWANKAR JAGDISH RAMCHANDRA	B-27/29,MIDC, PHASE 1, DOMBIVLI, DIST. THANE. PIN 421 203
4	DESAI JIGNESH RANJITRAI	B-27/29,MIDC, PHASE 1, DOMBIVLI, DIST. THANE. PIN 421 203

PCT International Classification Number

A01N43/88

PCT International Application Number

N/A

PCT International Filing date

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1			NA