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PROCESS FOR THE PREPARATION OF ROSUVASTATIN CALCIUM

IP.com Disclosure Number: IPCOM000244859D
Publication Date: 2016-Jan-22
Document File: 4 page(s) / 46K

Publishing Venue

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Abstract

The present disclosure provides a process for the preparation of rosuvastatin calcium.

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PROCESS FOR THE PREPARATION OF ROSUVASTATIN CALCIUM

Abstract

The present disclosure provides a process for the preparation of rosuvastatin calcium.

Reported herein is a process for the preparation of rosuvastatin calcium of Formula I,

Formula I

The reported process comprises:

(a)    treating an amine salt of rosuvastatin of Formula II

Formula II

wherein ‘R’ is a hydrogen or an alkyl group, with sodium hydroxide;

(b)   adjusting pH of the reaction mixture of step (a) to about 8.5 to about 9.0 using acetic acid;

(c)    treating the reaction mixture of step (b) with an aqueous ammonia solution;

(d)   reacting the reaction mixture of step (c) with a calcium salt; and

(e)    isolating rosuvastatin calcium of Formula I.

The term “amine salt,” as used herein, refers to a salt of ammonia, primary amines, secondary amines, tertiary amines, or cyclic amines.  Examples of primary amines include methyl amine, ethyl amine, 1-propyl amine, and 1-butyl amine.  Examples of secondary amines include 2-propyl amine and 2-butyl amine.  An example of a tertiary amine is 2-methylpropan-2-amine.  An example of a cyclic amine is cyclohexyl amine.

The term “alkyl,” as used herein, refers to methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 2-butyl, 2-methylpropyl, or cyclohexyl. 

The term “about,” as used herein, refers to any value which lies within the range defined by a number up to ±10% of the value.

The term “ambient temperature,” as used herein, refers to a temperature in the range of about 25°C to about 35°C.

The term “isolating,” as used herein, refers to precipitation, cooling, filtration, concentration, centrifugation, or combinations thereof, followed by drying.  Drying may be carried out under reduced pressure, vacuum tray drying, or air drying.

The treatment of the amine salt of rosuvastatin of Formula II with sodium hydroxide to obtain a sodium salt of rosuvastatin is carried out in water.  The sodium salt of rosuvastatin is treated with acetic acid until the pH is about 8.5 to about 9.0, followed by the treatment of the reaction mixture with an aqueous solution of ammonia to neutralize the excess of acetic acid.  The resulting mixture was reacted with an aqueous solution of a calcium salt to obtain rosuvastatin calcium.  Examples of the calcium salt include calcium chloride and calcium acetate.

An amine salt of rosuvastatin of Formula II can be prepared using the procedures described in PCT Publication Nos. WO 00/49014, WO 2007/125547, WO 2008/044243, or WO 2011/132172, which are incorporated herein by reference.

Examples

Comparative Example:

Preparation of rosuvastatin calcium (Formula I)

                 An aqueous solution of sodium hydroxide (0.72 g in 10 mL) was added to a solution of  (3R,5S,6E)-7-[4-(4-fluorophenyl)-2-[methyl(methylsulfonyl)amino]-6-(p...