Efficient process for production of carvedilol phosphate

• US 7,777,053 B2
• Filed: 11/07/2007
• Issued: 08/17/2010
• Est. Priority Date: 05/17/2007
• Status: Expired due to Fees

• Current Assignee: Wanbury Limited
• Original Assignee: Wanbury Limited
• Inventors: Zahid, Alam Sayyed, Sanganbhatla, Shankar, Suryavanshi, Jitendra Pandurang
• Primary Examiner(s): Shiao; Rei-tsang
• Application Number:
  US11/936,634
• Publication Number:
  US 20080287688A1
• Time in Patent Office: 1,014 Days
• Field of Search: 548/444
• US Class Current: 548/444
• CPC Class Codes: C07D 209/88 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the ring system

Abstract

A novel cost effective process for the synthesis of phosphate salts of 1-(9H-carbazol-4yloxy)-3-[[2-(2-methoxyphenoxy)ethyl]amino]-propan-2-ol, (carvedilol phosphate) of formula (II) with high yields and purity is disclosed. More particularly, the invention discloses a process for preparation of crystalline phosphate salts of carvedilol using various phosphate forming reagents such as phosphorous pentoxide, polyphosphoric acid, dipotassium hydrogen phosphate, ammonium dihydrogen ortho phosphate, and sodium dihydrogen ortho phosphate in solvents selected from Acetonitrile, acetone and tetrahydrofuran. The solvents used to prepare solvates of carvedilol dihydrogen phosphate are methanol, ethanol and isopropyl alcohol.

Claims

1. An efficient process for preparation of carvedilol dihydrogen phosphate hemihydrate salt in high yield comprising the steps of:

a) dissolving carvedilol free base in a suitable solvent and water mixture;

b) generating a phosphate salt of the carvedilol using a suitable phosphate forming agent selected from the group consisting of phosphorous pentoxide (phosphorus pentoxide), polyphosphoric acid, dipotassium hydrogen phosphate, ammonium dihydrogen ortho phosphate and sodium dihydrogen ortho phosphate to obtain carvedilol dihydrogen phosphate salt; and

c) isolating the carvedilol dihydrogen phosphate hemihydrate salt from the reaction mass.

2. The process as claimed in claim 1, wherein the phosphate forming agent used in the preparation of the salt comprises phosphorous pentoxide.

3. The process as claimed in claim 1, wherein the phosphate forming agent used in the preparation of the salt comprises polyphosphoric acid.

4. The process as claimed in claim 1, wherein the phosphate forming agent used in the preparation of the salt comprises dipotassium hydrogen phosphate.

5. The process as claimed in claim 1, wherein the phosphate forming agent used in the preparation of the salt comprises ammonium dihydrogen ortho phosphate.

6. The process as claimed in claim 1, wherein the phosphate forming agent used in the preparation of the salt comprises sodium dihydrogen ortho phosphate.

7. The process as claimed in claim 1, wherein said solvent used in the salt preparation is acetonitrile.

8. The process as claimed in claim 1, wherein said solvent used in the salt preparation is tetrahydrofuran.

9. The process as claimed in claim 1, wherein said solvent used in the salt preparation is acetone.

10. The process as claimed in claim 1, wherein carvedilol phosphate is isolated with a yield of at least about 93%.

11. The process as claimed in claim 1 wherein the generating is carried out at a temperature in the range from 35 to 50°

C. for a time period of 30 mins to 2 hrs.