| 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 M<SUP>+</SUP> wherein M<SUP>30 </SUP> is either a cation of an alkali metal or an ammonium cation of formula R<SUB>n</SUB>N<SUP>(+)</SUP>H<SUB>(4-n) </SUB>wherein R is lower C<SUB>1</SUB>-C<SUB>5 </SUB>alkyl, 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 C<SUB>1</SUB>-C<SUB>5 </SUB>alcoholate, to the hemi-calcium salt, and the latter is precipitated with a C<SUB>1</SUB>-C<SUB>5</SUB>hydrocarbon or dialkylether of formula R<SUB>1</SUB>OR<SUB>2</SUB>, wherein each of R<SUB>1 </SUB>and R<SUB>2 </SUB>is a C<SUB>1</SUB>-C<SUB>5 </SUB>alkyl 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. |
