Patent ID: 6605728
Filing Date: 2003-08-12
Classification: C07D

Abstract:
A factory scale process for producing crystalline atorvastatin trihydrate hemi calcium salt comprising the steps of:(a) reacting a mixture of atorvastatin lactone, methanol, and methyl tert-butyl ether with sodium hydroxide to form the ring-opened sodium salt; (b) forming a product rich aqueous layer and an organic layer comprising methyl tert-butyl ether containing impurities; (c) removing the organic layer comprising methyl tert-butyl ether containing impurities; (d) extracting the product rich aqueous layer with methyl tert-butyl ether; (e) adding an extra charge of methyl tert-butyl ether to a vessel containing the product rich aqueous layer in an amount of at least 1% w/v of the contents of the vessel; (f) sealing the reaction vessel; (g) heating the contents of the sealed reaction vessel to 47Â° C. to 57Â° C. in the presence of the extra charge of methyl tert-butyl ether which saturates the crystallization matrix on heating; (h) adding calcium acetate hemihydrate to the sealed reaction vessel to form atorvastatin trihydrate hemi calcium salt; (i) providing a vacuum pan dryer having an agitator; and (j) drying the isolated product in a vacuum pan dryer whilst continuously rotating the agitator at a speed of from 0.5 rpm to 2 rpm.