sodium (3R,5S,6E)-7-(4-(4-fluorophenyl)-2-(N-methylmethanesulfonamido)-6-(propan-2-yl)pyrimidin-5-yl)-3,5-dihydroxyhept-6-enoate → Rosuvastatin MethanaMine Salt

Participants

Reaction Steps

The obtained (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl](3R,5S)-3,5-dihydroxyhept-6-enoic acid sodium salt was dissolved in acetonitrile (100 ml), and purified water (190 ml) and a 1.0M hydrochloric acid aqueous solution (81 ml) were added thereto at 0° C., followed by stirring for 1 hour. Diisopropyl ether (250 ml) was added to the reaction liquid, followed by separation of the organic layer, and acetonitrile (81 ml) and a 40% methyl amine aqueous solution (7.3 ml) were added thereto at 0° C., followed by stirring at room temperature for 3 hours. The reaction liquid was stirred at 0° C. for 1 hour, and the precipitated solid was filtered, washed with acetonitrile (100 ml) and then dried under reduced pressure at 50° C. for 4 hours to give a (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl](3R,5S)-3,5-dihydroxyhept-6-enoic acid methylamine salt (10.25 g). Purified water (60 ml) was added to the solid to which a 2M sodium hydroxide aqueous solution (10 ml) was then added, followed by stirring for 1 hour, and the reaction solvent was distilled off under reduced pressure. Purified water (100 ml) was additionally added thereto, followed by another distillation under reduced pressure. To the resulting oil was added purified water (60 ml), and anhydrous calcium chloride (3.0 g) dissolved in purified water (10 ml) was added thereto, followed by stirring for 1 hour. The precipitated solid was filtered and washed with purified water (100 ml) to give the title compound (8.5 g, 77%). [α]D20 was +7.2 in 1% methanol, and the chiral purity was 99.9% ee, as confirmed by a HPLC method using the following chiral column.

Provenance & Evidence