Ethyl bromoacetate → 3-[3-(Ethoxycarbonylmethyl-amino)-4-methyl-phenyl]-piperidine-1-carboxylic acid benzyl ester

Participants

Reaction Steps

3-(3-Amino-4-methyl-phenyl)-piperidine-1-carboxylic acid benzyl ester (Example 13; 230 mg, 0.71 mmol) was dissolved in 5 mL dimethylformamide. Cesium carbonate (462 mg, 1.42 mol) and ethyl bromoacetate (86 μL, 0.78 mmol) were added and the mixture stirred at ambient temperature under a nitrogen atmosphere for 72 h. An additional 86 μL of ethyl bromoacetate were added and the reaction stirred an additional 24 h. The mixture was diluted with 100 mL water and extracted with diethyl ether (2×50 mL). The organic extracts were combined, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resultant oil was flash chromatographed with 20% ethyl acetate/hexanes to yield 152 mg (52%) of 3-[3-(ethoxycarbonylmethyl-amino)-4-methyl-phenyl]-piperidine-1-carboxylic acid benzyl ester as a clear oil.

Provenance & Evidence