Potassium Carbonate → (3R,4R)-3-hydroxy-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-piperidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

A solution of 16.50 g (56.24 mmol) of (3R,4R)-3-hydroxy-4-(4-hydroxy-phenyl)-piperidine-1-carboxylic acid tert-butyl ester in 40 ml of N,N-dimethylformamide was treated in succession with 12.68 g (59.06 mmol) of 1-(3-chloro-propoxymethyl)-2-methoxy-benzene (WO 97/09311) and 12.44 g (90.00 mmol) of potassium carbonate. This mixture was stirred at 120° C. for 26 hours. Subsequently, the salts were filtered off and washed with dichloromethane. The filtrate was concentrated in a high vacuum to eliminate most of the N,N-dimethylformamide, poured into 300 ml of an ice/water mixture and the aqueous phase was extracted three times with 100 ml of dichloromethane. The combined organic phases were washed once with a small amount of water, dried over magnesium sulphate, evaporated under reduced pressure and dried in a high vacuum. The thus-obtained crude product (31.64 g) was separated on silica gel using a 99:1 mixture of dichloromethane and methanol as the eluent and yielded 25.4 g (53.85 mmol, 95.8% of theory) of (3R,4R)-3-hydroxy-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-piperidine-1-carboxylic acid tert-butyl ester as a slightly yellow oil; MS: 489 (M+NH4+)+.

Provenance & Evidence