PREPARATION OF NON-CRYSTALLINE ATORVASTATIN CALCIUM

摘要

Atorvastatin, a substance with the chemical name hemi calcium salt of (R-(R*,R*))-2-(4-fluorophenyl)-beta, delta-dihydroxy-5-(1 methylethyl)-3-phenyl-4((enylamino)carbonyl)-1H-pyrrol-1-heptanoic acid, is known as the inhibitor of HMG-CoA reductase and has been used as an antihypercholesterolemic. Atorvastatin has been always prepared in the form of a calcium salt convenient for preparation of suitable pharmaceutical formulations such as pills, capsules, powders and other forms appropriate for oral administration. It can exist in the amorphous as well as one of the four crystalline forms (Form I, II, III, and IV). Atorvastatin is a very low water-soluble substance, but it has been found out that its crystalline forms are lower soluble than the amorphous one, a fact that may influence its bioavailability in the body. The submitted invention refers to a new procedure of direct transformation of an intermediate in the synthesis of atorvastatin 44a or 44 or atorvastatin lactone into the amorphous atorvastatin.