Cesium carbonate → 3-[3-(1-Ethoxycarbonyl-1-methyl-ethoxy)-4-methyl-phenyl]-piperidine-1-carboxylic acid benzyl ester

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-(3-hydroxy-4-methyl-phenyl)-piperidine-1-carboxylic acid benzyl ester (2.24 g, 6.88 mmol) in 15 mL dimethylformamide was added cesium carbonate (4.49 g, 13.77 mmol) and ethyl-2-bromoisobutyrate (4.04 mL, 27.53 mmol). The mixture was heated to 60° C. under N2 with stirring for 18 h and cooled to ambient temperature. The resultant brown suspension was diluted with 300 mL water and extracted with diethyl ether (2×200 mL). The organic phases were combined and dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resultant oil was flash chromatographed with 20% ethyl acetate/hexanes to yield 1.36 g (45%) of the desired 3-[3-(1-ethoxycarbonyl-1-methyl-ethoxy)-4-methyl-phenyl]-piperidine-1-carboxylic acid benzyl ester as a clear oil.

Provenance & Evidence