Isopropanol → Nilvadipine

Participants

Reaction Steps

Phosphorus pentachloride (2.46 g) was added to a suspension of (+)-methyl 5-carboxy-2-cyano-6-methyl-4-(3-nitrophenyl) -1,4-dihydropyridine-3-carboxylate (3.12 g) in methylene chloride (30 ml) under ice-cooling, and the mixture was stirred for 30 minutes. Then, a solution of isopropyl alcohol (1.4 g) in methylene chloride (10 ml) was added dropwise thereto over a period of 10 minutes. After being stirred for 20 minutes, 5% aqueous sodium carbonate (30 ml ) was added to the reaction solution and then stirred at ambient temperature for an hour. The organic layer was separated and the aqueous layer was extracted with methylene chloride. The combined organic layer was washed with brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by column chromatography on silica gel (75 g) using a mixture of benzene and ethyl acetate (10:1) as an eluent. The eluate was evaporated in vacuo and the residue was crystallized from diisopropyl ether to give (+)-5-isopropyl 3-methyl 2-cyano-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate (3.34 g).

Provenance & Evidence