Carbon tetrabromide → (R)-ethyl 4-(4-((4'-chlorobiphenyl-2-yl)(diethoxyphosphoryloxy)methyl)piperidin-1-yl)benzoate

Participants

Reaction Conditions

Reaction Steps

A solution of (R)-ethyl 4-(4-((4′-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoate (INTERMEDIATE 11A, 600 mg, 1.33 mmol), CBr4 (575 mg, 1.73 mmol), and pyridine (2 ml) at 0° C. was treated dropwise over a 10 minute period with triethyl phosphite (0.56 ml, 3.33 mmol). The solution was stirred at 0° C. for about 10 minutes and then the ice bath was removed. The reaction was stirred overnight at r.t. whereupon the excess pyridine was removed under reduced pressure and the concentrate was taken up in 50 ml of DCM. The organic layer was washed successively with 50 ml each of 0.5 N aq. HCl, saturated aqueous sodium bicarbonate, and water. The organic layers were dried over sodium sulfate, filtered and adsorbed onto silica gel. Purification by column chromatography (ISCO, 80 g silica gel column, eluting with 0→100% EtOAc/hexanes over 24 minutes) gave the title compound (500 mg, yield: 64%).

Provenance & Evidence