Hydrogen Peroxide → (3S,4S)-4-(4-benzyloxy-phenyl)-1-((R)-1-phenyl-ethyl)-piperidin-3-ol

Participants

Reaction Conditions

Reaction Steps

The reaction flask was charged under argon with 60 g (162 mmol) of (R)-4-(4-benzyloxy-phenyl)-1-(1-phenyl-ethyl)-1,2,3,6-tetrahydro-pyridine and 600 mL of dimethoxyethane. After addition of 9.2 g (243 mmol) of sodium-borohydride the mixture was cooled to 0° C. under stirring. Then 45.9 g (323 mmol) of borontrifluoride-diethyletherate was added during 40 min, wherein the temperature was kept at 0-5° C. The reaction mixture was stirred at 5° C. for additional 2 h and then at room temperature for 165 min. After cooling to 0° C., 350 mL of 4 N NaOH was added during 1 h, wherein the temperature was kept at 5-10° C. Then 60 mL of 30% H2O2 was added at 20° C. during 1 h. After additional stirring for 20 min the mixture was heated to 45° C., which caused the temperature to raise temporarily to 55° C. After cooling, the temperature was kept at 45° C. for a total of 3 h. After stirring overnight at room temperature the reaction mixture was poured into a mixture of 1 L half-saturated NaCl solution and 800 mL of ethyl acetate. After extraction with ethyl acetate the organic phases were washed with water and dried over Na2SO4. After concentration, 67.4 g of the diastereomeric mixture of (3R,4R)-4-(4-benzyloxy-phenyl)-1-((R)-1-phenyl-ethyl)-piperidin-3-ol and (3S,4S)-4-(4-benzyloxy-phenyl)-1-((R)-1-phenyl-ethyl)-piperidin-3-ol were obtained in a ratio of 3:1.

Provenance & Evidence