method of producing an amorphous form of hemicalciumsalzes of (3r, 5r) - 7 - phenyl - 4 - phenyl - 2 - carbamoyl (four countries) - 5 - isopropyl pyrrol 1 ylu00fc - 3.5 - dihydroxy heptane acid (atorvastatin)

摘要

A method of manufacturing an amorphous form of the hemi-calcium salt of (3R, 5R) 7-[3-phenyl-4-phenylcarbamoyl-2-(4-fluorophenyl)-5-isopropyl-pyrrol-1-yl]-3,5-dihydroxyheptanoic acid of formula (I), in which (3R, 5R) 7-[3-phenyl-4-phenylcarbamoyl-2-(4-fluorophenyl)-5-isopropyl-pyrrol-1-yl]-3,5-dihydroxyheptanoic acid or its salt with a cation MSUP+/SUP wherein MSUP30 /SUP is either a cation of an alkali metal or an ammonium cation of formula RSUBn/SUBNSUP(+)/SUPHSUB(4-n) /SUBwherein R is lower CSUB1/SUB-CSUB5 /SUBalkyl, n may reach values ranging between 0 and 3, is, without isolating the intermediate in the form of the hemi-calcium salt or of another salt, acid or lactone, converted, in a solution, by the treatment with the calcium salt or calcium hydroxide, or a calcium CSUB1/SUB-CSUB5 /SUBalcoholate, to the hemi-calcium salt, and the latter is precipitated with a CSUB1/SUB-CSUB5/SUBhydrocarbon or dialkylether of formula RSUB1/SUBORSUB2/SUB, wherein each of RSUB1 /SUBand RSUB2 /SUBis a CSUB1/SUB-CSUB5 /SUBalkyl group. The starting acid or its salt is prepared starting from (3R, 5R) tert-butyl (6-{2-[3-phenyl-4-phenylcarbamoyl-2-(4-fluorophenyl)-5-isopropyl-pyrrol-1-yl]-ethyl}-2,2-dimethyl-[1,3]dioxane-4-yl) acetate of formula II.