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“Improved Process For The Preparation Of Benzenaecetic Acid, A Methyl 3 Phenoxy , Calcium Salt Dihydrate, (Fenoprofen Calcium)”

Abstract: The present invention relates to an improved process for the preparation of Fenoprofen calcium (1). Further, the present invention provides Fenoprofen calcium (1) having purity greater than 99.0 %.

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Patent Information

Application #
Filing Date
16 September 2019
Publication Number
12/2021
Publication Type
INA
Invention Field
CHEMICAL
Status
Email
radha@biophore.com
Parent Application

Applicants

Biophore India pharmaceuticals Pvt. Ltd
Plot#92; 1-98/2/92, Kavuri Hills – Phase II, Jubilee Hills, Hyderabad, Telangana India-500033.

Inventors

1. Manik Reddy Pullagurla
Plot#92; 1-98/2/92, Kavuri Hills – Phase II, Jubilee Hills, Hyderabad, Telangana India-500033.
2. Bhaskar Reddy Pitta
Plot#92; 1-98/2/92, Kavuri Hills – Phase II, Jubilee Hills, Hyderabad, Telangana India-500033.
3. Jagadeesh Babu Rangisetty
Plot#92; 1-98/2/92, Kavuri Hills – Phase II, Jubilee Hills, Hyderabad, Telangana India-500033.

Specification

1. A process for the preparation of Fenoprofen calcium (1) with purity greater
than 99.0% by HPLC, comprising:
a) reducing 1-(3-phenoxyphenyl) ethanone (6) with a suitable reducing agent to form 1-(3-phenoxyphenyl) ethanol (5);
b) chlorinating intermediate (5) using a suitable chlorinating agent to form 1-(1-chloroethyl)-3-phenoxybenzene (4);
c) converting intermediate (4) to 2-(3-phenoxyphenyl) propanenitrile (3);
d) converting intermediate (3) to sodium 2-(3-phenoxyphenyl) propanoate (2) in presence of a suitable base; and
e) converting sodium 2-(3-phenoxyphenyl) propanoate (2) to Fenoprofen calcium (1).

2. The process according to claim 1, wherein the suitable reducing used in step a) is selected from a group comprising of lithium aluminum hydride (LiAlH4), sodium borohydride (NaBH4), sodium cyanoborohydride (NaBH3CN), sodium triacetoxyborohydride (NaBH (CH₃COO)₃), sodium borohydride (NaBH4), lithium cyanoborohydride, tetrabutylammonium cyanoborohydride ((CH3CH2CH2CH2)4N(BH3CN)), tetramethylammonium triacetoxyborohydride (NMe4BH(OAc)3.
3. The process according to claim 1, wherein the suitable chlorinating agent used in step b) is ammonium chloride.
4. The process according to claim 1, wherein the suitable base used in step d) used is selected from a group comprising of sodium hydroxide, potassium hydroxide, lithium hydroxide ,sodium carbonate, potassium carbonate, lithium carbonate, sodium bicarbonate, potassium bicarbonate, lithium bicarbonate, sodium methoxide, sodium ethoxide, sodium tert-butoxide, potassium methoxide, potassium ethoxide, potassium tert-butoxide, or mixtures thereof .
5. The process according to claim 1, wherein the suitable solvent used in the present invention is protic or aprotic solvents or its mixture selected from

the group comprising of methanol, ethanol, propanol, isopropanol, butanol, water, acetone, acetonitrile, benzene, dichloromethane, ethyl acetate, acetone, dichloromethane dimethylformamide, dimethyl sulfoxide, toulene, tetrahydrofuran or mixtures thereof.
6. A process for the preparation of Fenoprofen calcium (1) with purity
1. reducing 1-(3-phenoxyphenyl) ethanone (6) with a suitable reducing agent to form 1-(3-phenoxyphenyl) ethanol (5);
2. brominating intermediate (5) using a suitable chlorinating agent to form 1-(1-bromoethyl)-3-phenoxybenzene (9);
3. converting intermediate (9) to 2-(3-phenoxyphenyl) propanenitrile (3);
4. converting intermediate (3) to sodium 2-(3-phenoxyphenyl) propanoate (2) in presence of a suitable base; and
5. converting sodium 2-(3-phenoxyphenyl) propanoate (2) to Fenoprofen calcium (1).

7. The process according to claim 6, wherein the intermediate 1-(3-phenoxyphenyl) ethanone (6) used is prepared by heating 3-hydroxy acetophenone (8) with bromobenzene (7) in presence of potassium carbonate and metal catalyst, copper bronze.
8. The process according to claim 1, wherein the Fenoprofen calcium (1) obtained is having purity greater than 99.0% and total impurities less than 1% (w/w).
9. The process according to claim 1, wherein the Fenoprofen calcium (1) obtained is having characteristic X-Ray powder diffraction as shown in

Documents

Application Documents

# Name Date
1 201941037162-FER.pdf 2025-04-30
1 201941037162-PROVISIONAL SPECIFICATION [16-09-2019(online)].pdf 2019-09-16
2 201941037162-FORM 18 [09-09-2023(online)].pdf 2023-09-09
2 201941037162-FORM FOR SMALL ENTITY(FORM-28) [16-09-2019(online)].pdf 2019-09-16
3 201941037162-FORM FOR SMALL ENTITY [16-09-2019(online)].pdf 2019-09-16
3 201941037162-COMPLETE SPECIFICATION [16-09-2020(online)].pdf 2020-09-16
4 201941037162-FORM 1 [16-09-2019(online)].pdf 2019-09-16
4 201941037162-DRAWING [16-09-2020(online)].pdf 2020-09-16
5 201941037162-EVIDENCE FOR REGISTRATION UNDER SSI(FORM-28) [16-09-2019(online)].pdf 2019-09-16
5 201941037162-ENDORSEMENT BY INVENTORS [16-09-2020(online)].pdf 2020-09-16
6 201941037162-EVIDENCE FOR REGISTRATION UNDER SSI [16-09-2020(online)].pdf 2020-09-16
6 201941037162-EVIDENCE FOR REGISTRATION UNDER SSI [16-09-2019(online)].pdf 2019-09-16
7 201941037162-FORM 3 [16-09-2020(online)].pdf 2020-09-16
7 201941037162-DRAWINGS [16-09-2019(online)].pdf 2019-09-16
8 Correspondence by Applicant_Form1-Form28_30-09-2019.pdf 2019-09-30
8 201941037162-FORM FOR SMALL ENTITY [16-09-2020(online)].pdf 2020-09-16
9 201941037162-FORM FOR SMALL ENTITY [16-09-2020(online)].pdf 2020-09-16
9 Correspondence by Applicant_Form1-Form28_30-09-2019.pdf 2019-09-30
10 201941037162-DRAWINGS [16-09-2019(online)].pdf 2019-09-16
10 201941037162-FORM 3 [16-09-2020(online)].pdf 2020-09-16
11 201941037162-EVIDENCE FOR REGISTRATION UNDER SSI [16-09-2019(online)].pdf 2019-09-16
11 201941037162-EVIDENCE FOR REGISTRATION UNDER SSI [16-09-2020(online)].pdf 2020-09-16
12 201941037162-ENDORSEMENT BY INVENTORS [16-09-2020(online)].pdf 2020-09-16
12 201941037162-EVIDENCE FOR REGISTRATION UNDER SSI(FORM-28) [16-09-2019(online)].pdf 2019-09-16
13 201941037162-DRAWING [16-09-2020(online)].pdf 2020-09-16
13 201941037162-FORM 1 [16-09-2019(online)].pdf 2019-09-16
14 201941037162-COMPLETE SPECIFICATION [16-09-2020(online)].pdf 2020-09-16
14 201941037162-FORM FOR SMALL ENTITY [16-09-2019(online)].pdf 2019-09-16
15 201941037162-FORM 18 [09-09-2023(online)].pdf 2023-09-09
15 201941037162-FORM FOR SMALL ENTITY(FORM-28) [16-09-2019(online)].pdf 2019-09-16
16 201941037162-FER.pdf 2025-04-30
16 201941037162-PROVISIONAL SPECIFICATION [16-09-2019(online)].pdf 2019-09-16
17 201941037162-POA [24-10-2025(online)].pdf 2025-10-24
18 201941037162-FORM-26 [24-10-2025(online)].pdf 2025-10-24
19 201941037162-FORM FOR SMALL ENTITY [24-10-2025(online)].pdf 2025-10-24
20 201941037162-FORM 13 [24-10-2025(online)].pdf 2025-10-24
21 201941037162-EVIDENCE FOR REGISTRATION UNDER SSI [24-10-2025(online)].pdf 2025-10-24
22 201941037162-AMENDED DOCUMENTS [24-10-2025(online)].pdf 2025-10-24
23 201941037162-FER_SER_REPLY [27-10-2025(online)].pdf 2025-10-27
24 201941037162-DRAWING [27-10-2025(online)].pdf 2025-10-27
25 201941037162-CLAIMS [27-10-2025(online)].pdf 2025-10-27
26 201941037162-ABSTRACT [27-10-2025(online)].pdf 2025-10-27

Search Strategy

1 201941037162_SearchStrategyNew_E_201941037162E_29-04-2025.pdf