4-Methylmorpholine → 1-Boc-4-(2-(4-Fluoro-3-(trifluoromethyl)phenyl)-2-oxoethylcarbamoyl)piperidine

Participants

Reaction Conditions

Reaction Steps

To a solution of piperidine-1,4-dicarboxylic acid mono-tert-butyl ester (9611.92 mg; 41.92 mmol; 1.08 eq.) in THF 100 ml, added 4-methyl-morpholine (14.51 ml; 131.98 mmol; 3.40 eq.), The reaction mixture was cooled to −10° C., 3-methyl-butyryl chloride (5.03 ml; 38.82 mmol; 1.00 eq.) was add dropwise and maintaining the temperature below −5° C. after stirring for 30 mins at from −5° C. to 10° C., 2-(4-Fluoro-3-trifluoromethyl-phenyl)-2-oxo-ethyl-ammonium chloride (10.00 g; 38.82 mmol; 1.00 eq.) was added at −5° C. and stirred the mixture for 20 mins and then RT for 1 h. Added brine, extracted with EA, washed with brine, dried and concentrated. The crude oil was treated with ether. The white solid was collected as the title compound (12 g, yield 71.5%).

Provenance & Evidence