Sodium hydride → HCID 57079772, compound

Participants

Reaction Conditions

Reaction Steps

To an ice-cooled solution of 3.50 g (6.13 mmol) of the (3R,4R)-4-[4-(3-methanesulfonyloxy-propoxy)-phenyl]-3-(quinolin-7-ylmethoxy)-piperidine-1-carboxylic acid tert-butyl ester and 4.97 ml (4.42 g, 61.33 mmol, 10.0 equiv.) of cyclopropyl carbinol in 25 ml of tetrahydrofuran was added 0.535 g (12.27 mmol, 2.0 equiv.) of sodium hydride dispersion (55% in mineral oil) in portions. The mixture was warmed to 55° C. and stirred for 1.5 h. The reaction mixture was poured into 200 ml of an ice/water mixture, the pH was adjusted to 8 by addition of saturated sodium bicarbonate solution, and the aqueous phase was extracted four times with 200 ml of ethyl acetate. The combined organic phases were washed twice with 25 ml of water, evaporated under reduced pressure and dried in a high vacuum. The thus obtained crude product was purified by chromatography on silica gel using a 1:2 v/v mixture of hexane and ethyl acetate as eluent to yield 3.32 g (6.07 mmol, 99.0% of theory) of the (3R,4R)-4-[4-(3-cyclopropylmethoxy-propoxy)-phenyl]-3-(quinolin-7-ylmethoxy)-piperidine-1-carboxylic acid tert-butyl ester as a colorless oil; MS: 547 (M+H)+.

Provenance & Evidence