IP Library Granted Patent US 9,273,333
Granted Patent B2
US 9,273,333 · App. 14/288,999 · Granted Mar 1, 2016

Process for the preparation of intermediates of HMG-CoA reductase inhibitors

Inventors: Michiel Christian Alexander Van Vliet (Hyderabad, IN); Willem Robert Klaas Schoevaart (Hyderabad, IN); Madhuresh Kumar Sethi (Hyderabad, IN); Sanjay Mahajan (Hyderabad, IN); Bhairaiah Mara (Hyderabad, IN)
Assignee: Mylan Laboratories LTD
C12P17/12C07C231/12C07D215/14C07D239/42C07F7/1844C12P7/42C12P7/44C12P7/62C12P9/00C12P13/02
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Quick Facts
Patent No.
US 9,273,333
App. No.
14/288,999
Granted
Mar 1, 2016
Kind
B2
Abstract

The present invention relates to an improved process for the preparation of compound of Formula-II, which is an intermediate in the preparation of HMG-CoA reductase inhibitors. wherein X is hydrogen or hydroxy protecting group and R 1 is carboxyl protecting group.

Claims (18)

1. A process for the preparation of compound of Formula-II comprising the steps of:

a) enzymatic enantioselective amidation of compound of Formula-III in presence of suitable enzyme to get amide compound of Formula-IV

wherein R 2 is C 1 -C 5 alkyl or aryl or arylalkyl group and wherein said suitable enzyme is Candida Antartica lipase;

b) transesterification of compound of Formula-IV into compound of Formula-V

wherein R 3 is C 1 -C 5 alkyl or aryl or arylalkyl group with proviso that R 3 is different than R 2 of Formula-IV;

c) protecting the hydroxy group with suitable hydroxy protecting group to get compound of Formula-VI

wherein X is a suitable protecting group;

d) converting the compound of Formula-VI into compound of Formula-VII; and

e) converting compound of Formula-VII into compound of Formula-II

wherein R 1 is carboxyl protecting group and X is defined above.

2. The process according to claim 1 , wherein lipase is Candida Antartica lipase B.

3. The process according to claim 1 , wherein R 3 is arylalkyl group in compound of Formula-V.

4. The process according to claim 1 , wherein transesterification of the compound of Formula-IV is carried out in presence of catalyst.

5. The process according to claim 4 , wherein catalyst is selected from tetramethyl orthotitanate, tetraethyl orthotitanate, tetrapropyl orthotitanate, tetraisopropyl orthotitanate, tetrabutyl orthotitanate or tetrabenzyl orthotitanate.

6. The process according to claim 1 , wherein compound of Formula-VI is converted into compound of Formula-VII by catalytic hydrogenation.

7. The process according to claim 1 , wherein R 1 is C 1 -C 5 alkyl group in compound of Formula-II.

8. The process according to claim 1 , wherein compound of Formula-II is further converted into HMG-CoA reductase inhibitors.

9. The process according to claim 8 , wherein the HMG-CoA reductase inhibitor is Rosuvastatin or Pitavastatin.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 6, 2024
From: MYLAN LABORATORIES LIMITED
To: TIANISH LABORATORIES PRIVATE LIMITED
Reel/Frame 068861/0150 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 23, 2015
From: VAN VLIET, MICHIEL CHRISTIAN ALEXANDER; SCHOEVAART, WILLEM ROBERT KLAAS; SETHI, MADHURESH KUMAR; MAHAJAN, SANJAY; MARA, BHAIRAIAH
To: MYLAN LABORATORIES LTD
Reel/Frame 036012/0171 →
Continuity (2)
Continuation PCTIN2012000770 · Nov 26, 2012
Related Publication 20140349350A1 · Nov 27, 2014