Ethyl bromoacetate → (3RS,4RS)-3-(1-ethoxycarbonylmethyl-1,2,3,4-tetrahydro-quinolin-7-ylmethoxy)-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-piperidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

A solution of 0.67 g (1.09 mmol) of (3RS,4RS)-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-3-(1,2,3,4-tetrahydro-quinolin-7-ylmethoxy)-piperidine-1-carboxylic acid tert-butyl ester in 10 ml of absolute N,N-dimethylformamide was successively treated at 0° C. with 0.21 g (1.30 mmol, 1.2 equiv.) of ethyl bromoacetate and 0.057 g (1.30 g, 1.30 mmol, 1.2 equiv.) of sodium hydride dispersion (55% in mineral oil). The mixture was then stirred for 2 h at 80° C. Then 0.047 g (1.09 mmol, 1.0 equiv.) of sodium hydride suspension (55% in mineral oil) and 0.18 g (1.09 mmol, 1.0 equiv.) of ethyl bromoacetate was added, and the suspension was stirred for another 8 h at 80° C. Subsequently, the suspension was poured into 100 ml of an ice/water mixture and extracted three times with 50 ml of ethyl acetate. The combined organic phases were washed three times with 20 ml of water, dried over magnesium sulphate, evaporated under reduced pressure and dried in a high vacuum. The thus-obtained crude product was purified by chromatography on silica gel using a 19:1 mixture of dichloromethane and ethyl acetate as the eluent and yielded 0.25 g (0.36 mmol, 33.0% of theory) of (3RS,4RS)-3-(1-ethoxycarbonylmethyl-1,2,3,4-tetrahydro-quinolin-7-ylmethoxy)-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-piperidine-1-carboxylic acid tert-butyl ester as a light yellow oil; MS: 703 (M+H)+.

Provenance & Evidence