Sodium cyanoborohydride → Risperidone

Participants

Reaction Steps

To a suspension of 1.39 g (3,42 mmoles) of 3-{2-[4-(6-fluorobenzo[d]isoxazol-3-yl)-piperidin-1-yl]-vinyl}-2-methyl-6,7,8,9-tetrahydro-pyrido[1,2-a]pyrimidin-4-one (III) in 22 mL of absolute ethanol and 1 mL of glacial acetic acid under stirring at room temperature and in a protective atmosphere, 0.254 g (4.04 mmoles) of sodium cyanoborohydride in small portions was added for 1 hour. After 1.5 hour, the solvent was evaporated and the crude product obtained was dissolved in 250 mL of ethyl acetate. The organic phase was successively washed with 50 mL of 1M aqueous sodium bicarbonate solution, 50 mL of water and 50 mL of saturated sodium chloride solution and dried over anhydrous magnesium sulphate. The resultant solution was filtered and the solvent was evaporated to yield 1.17 g of a residual solid (83%), which was diluted in methylene chloride and purified by column chromatography (silica gel). Elution of the column was with methylene chloride, methanol and triethylamine (95:5:1). The pure fractions were collected and the solvent was evaporated under reduced pressure to give 0.83 g (70.9%) of 3-{2-[4-(6-fluorobenzo[d]isoxazol-3-yl)-piperidin-1-yl]-ethyl}-2-methyl-6,7,8,9-tetrahydro-4H-pyrido-[1,2-a]pyrimidin-4-one (I). Optionally, the reaction crude product was purified by crystallization from a suitable organic solvent, preferably ethanol or 4-methyl-2-pentanone.

Provenance & Evidence