| Title of Invention | A PROCESS FOR PREPARAING 3-(HYDROXY-PENTYLIDENCE)-5-NITRO-3H-BENZOFURAN-2-ONE |
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| Abstract | (57) Abstract: A process for preparing 3-(hydroxy-pentylidene)-5-one comprising reacting 5-nitro-3H-benzofuran-2-one with p sah of pentanoic acid at a temperature in the range of 30°' the same from the reaction mixture in a known manner. PRICE: THIRTY RUP |
| Full Text | The present invention relates to 3-{1-hydroxy'pentylidene)-5-nitro-3H-benzofuran-2-one and to its ketonic tautomer form 3-(1-oxo-pentyl)'5-nitro-3H-benzofuran-2-one, 3-(1-hydroxy-pentylidene)-5-nitro-3H-benzofuran-2-one is a new compound which may be used as a synthesis intermediate. In particular, it may be converted to 2-butyl'5-nitrobenzofuran by hydrolysis, decarboxylation and cyclisation, by simple heating in an acid medium. 2-butyl-5-nitrobenzofuran may act as an intermediate in the synthesis of an antiarrythmic, dronedarone. The present invention provides, therefore, 3-(1-hydroxy-pentylidene)-5-nitro-3H-benzofuran-2-one corresponding to formula (!) and its ketonic tautomer form, 3-(1-oxo-pentyl)-5-nitro-3H-benzofuran-2-one corresponding to formula {II) may be prepared extemporaneously, preferably in situ, from pentanoic acid and a base. The base may be sodium carbonate. In the implementation of the process according to the invention, the resulting reaction mixture is brought into contact with an acid. This acid will be preferably dikite sulfuric acid", indeed, it permits better recover, of the expected final product. Still under preferential conditions for carrying out the process, the crude product obtained may be recrystaltised in an acid. This acid will be advantageouslv acetic acid. The present invention also provides the use of the product corresponding to formula (1) or its tautomenc fonn (11) for the production of synthesis intennediates. In particular, it provides the production of 2-buty-5-nitro-benzofuran-2-one wiiich may act as an mtermediate in the svnthcsis of an antiarrhythmic. dronedarone. Accordingly, the present invention provides a process tor preparing 3-(l- hvdrox>'-pentylidene)-5-nitro-3H-benzofuran-2-one of formula I or its ketonic . -I tautomer of formula II m comprising the step of reacting 5-nitro-3H-benzoluran-2-one with pentanoic anhydride and a sah of pentanoic acid optionally in the presence of pentanoic acid at a temperature above 30'C acidifying the reaction mixture and isolating the reaction product therefrom in a known manner. may be prepared extemporaneously, preferably in situ, from pentanoic acid and a base. The base may be sodium carbonate. In the implementation of the process according to the invention, the resulting reaction mixture is brought into contact with an acid. This acid will be preferably dilute sulfuric acid; indeed, it permits better recovery of the expected final product. Still under preferential conditions for carrying out the process, the crude product obtained may be recrystallised in an acid. This acid will be advantageously acetic acid. The present invention also provides the use of the product corresponding to formula (I) or its tautomeric form (II) for the production of synthesis intermediates. In particular, it provides the production of 2-butyl-5-nitro-benzofuran-2-one which may act as an intermediate in the synthesis of an antiarrhythmic, dronedarone. The examples below will permit a better understanding of the invention. EXAMPLE 1 The following are charged to a three-necked flask: 478.7 g (2.57 moles) of pentanoic anhydride 131.3 g (1.285 moles) of pentanoic acid 81.6 g (0.771 mole) of sodium carbonate 230 g (1.285 moles) of 5-nitro-3H-benzofuran-2-one and the mixture is raised to a temperature of 80°C for a period of 6 hours, with stirring. The mixture is cooled to 20°C and the following are added gradually within 15 minutes: 377.8 g (0.771 mole) of sulfuric acid diluted to 20%. The temperature of the mixture rises to about 40°C. The suspension is then cooled to 20°C and the precipitate is filtered. It is washed with 250 ml of deionised water then with 250 ml of heptane. WE CLAIM: 1. A process for preparing 3-{l-hydroxy-pentylidene)-5-nitro-3H-benzofuran-2-one of formula I or its ketonic tautomer of formula II comprising the step of reacting 5-mtro-3H-benzofuran-2-one with pentanoic anhydride and a salt of pentanoic acid optionally in the presence of pentanoic acid at a temperature in the range of 30°C to S0°C acidifying the reaction mixture and isolating the reaction product therefrom in a known manner. 2. The process as claimed in claim 1 wherein 1 mole of 5-nitro-3H-benzofuran-2- one is reacted with 1 to 5 moles of pentanoic anhydride. 0.1 to 2 motes of a salt of pentanoic acid and 0 to 1.5 moles of pentanoic acid, the resulting reaction nuxture is acidified and the reaction product is isolated in a known maimer. 3. 'The process as claimed in claim 1 or 2 wherein 1 mole of 5-nitro-3H-benzofuran-2-one is reacted with 2 moles of pentanoic anhydride and 1 mole of a salt of pentanoic acid, then the resulting reaction mixture is acidified, and then the reaction product is isolated. 4. The process as claimed in claims 1 to 3 wherein the salt of pentanoic acid is the salt of sodium, potassium or a salt of tertiary amine. 5, The process as claimed in claims 1 to 4 wherein the salt of pentanoic acid is produced extemporaneously from pentanoic acid and an organic or inorganic base. 6, The process as claimed in claims 1 to 5 wherein the salt of pentanoic acid is produced in situ from pentanoic acid and sodium carbonate. 7. The process as claimed in claims 1 to 6 wherein the reaction mixture is acidified vvith sulfuric acid. 8. The process as claimed in claims 1 to 7 wherein the reaction product (I) or its tautomeric form (II) is purified by recrystailisation in acetic acid. A process for preparing 3-(l-hydroxy-pentyIidene)-5-nitro-3H-benzofuran-2-one substantially as herein described and exemplified. |
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21-mas-2001 correspondence others.pdf
21-mas-2001 correspondence po.pdf
21-mas-2001 description (complete).pdf
| Patent Number | 193200 | |||||||||
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| Indian Patent Application Number | 21/MAS/2001 | |||||||||
| PG Journal Number | 30/2009 | |||||||||
| Publication Date | 24-Jul-2009 | |||||||||
| Grant Date | 15-Mar-2005 | |||||||||
| Date of Filing | 05-Jan-2001 | |||||||||
| Name of Patentee | CLARIANT | |||||||||
| Applicant Address | 70 AVENUE DU GENERAL DE GAULLE, 92800 PUTEAUX | |||||||||
Inventors:
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| PCT International Classification Number | C07D307/78 | |||||||||
| PCT International Application Number | N/A | |||||||||
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