Invention Grant
- Patent Title: Process for preparation of duloxetine hydrochloride
- Patent Title (中): 盐酸度洛西汀的制备方法
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Application No.: US12530214Application Date: 2008-03-05
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Publication No.: US08269023B2Publication Date: 2012-09-18
- Inventor: Rajinder Singh Siyan , Sunil Kumar Vinubhai Gohel , Girij Pal Singh
- Applicant: Rajinder Singh Siyan , Sunil Kumar Vinubhai Gohel , Girij Pal Singh
- Applicant Address: IN Mumbai
- Assignee: Lupin Ltd.
- Current Assignee: Lupin Ltd.
- Current Assignee Address: IN Mumbai
- Agency: Akerman Senterfitt
- Agent Peter A. Chiabotti
- Priority: IN312/KOL/2007 20070305; IN1172/KOL/2007 20070827; IN1343/KOL/2007 20070827
- International Application: PCT/IN2008/000125 WO 20080305
- International Announcement: WO2008/107911 WO 20080912
- Main IPC: C07D333/16
- IPC: C07D333/16

Abstract:
An improved process for synthesis of duloxetine hydrochloride (1) having chiral purity greater than 99.9% that is characterized by the following: (i) preparation of racemic condensed compound (RS)—N,N-di methyl-3-(1-naphthyloxy)-3-(2-thienyl)propanamine (4) by reaction of racemic hydroxy compound (2) with 1-fluoronaphthalene (3) in presence of a base such as sodamide, potassium amide or potassium bis(trimethylsilyl)amide (KHDMS) in polar aprotic solvent, (ii) optical resolution of racemic condensed compound (5a+5b) with di-benzoyl-L-tartaric acid (7, DBTA, R=H) or di-para-anisoyl-L-tartaric acid (7, DATA, R=OCH3) to obtain crude (S)—N.N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propanamine dibenzoyl tartarate salt (8a) or (S)—N.N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propanamine di-p-anisoyl tartarate salt (9a) respectively, (iii) optionally purification of crude tartarate salts (8a or 9a) by crystallization, (iv) optionally purification of duloxetine hydrochloride (1) by crystallization and (v) racemization of undesired (R)—N,N-di methyl-3-(1-naphthyloxy)-3-(2-thienyl)propanamine (5b) by treatment with base potassium bis(trimethylsilyl)amide (KHDMS) to obtain racemic mixture of condensed compounds (5a and 5b).
Public/Granted literature
- US20100105925A1 NOVEL PROCESS FOR PREPARATION OF DULOXETINE HYDROCHLORIDE Public/Granted day:2010-04-29
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