Oxalyl chloride → Oxalyl chloride

Participants

Reaction Steps

Oxalyl chloride (42 μL, 0.47 mmol) was added to a solution of 1-methylethyl 4-[({6-[4-(hydroxymethyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate (0.165 g, 0.43 mmol) in CH2Cl2 (5 mL) and DMF (0.5 mL) at 0° C. The mixture was warmed to ambient temperature and stirred for 1 h. Removal of CH2Cl2 and excess of oxalyl chloride under reduced pressure gave crude 1-methylethyl 4-[({6-[4-(chloromethyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate as a dark brown oil. Crude 1-methylethyl 4-[({6-[4-(chloromethyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate was mixed with sodium thiomethoxide (64 mg, 0.86 mmol) in DMF and heated at 100° C. overnight. Additional sodium thiomethoxide (64 mg, 0.86 mmol) was added, and the heating was continued at 100° C. overnight. Cooled to ambient temperature, the mixture was poured into water and extracted with Et2O. The combined organic extract was washed with water, brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give a yellow solid. The crude material was purified by chromatography on a silica gel column eluted with 1:11 EtOAc/CH2Cl2 to 1:8 EtOAc/CH2Cl2 to give 32 mg (18%) of 1-methylethyl 4-{[(6-{4-[(methylthio)methyl]phenyl}-3-pyridinyl)oxy]methyl}-1-piperidinecarboxylateas a white solid. LRMS (ESI), m/z 415 (M+H).

Provenance & Evidence