3-Bromo-1-propanol → (3R,4R)-3-[1-(3-hydroxy-propyl)-1,2,3,4-tetrahydro-quinolin-7-ylmethoxy]-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-piperidine-1-carboxylic acid tert-butyl ester

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Reaction Steps

A solution of 2.08 g (3.37 mmol) of (3R,4R)-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-3-(1,2,3,4-tetrahydro-quinolin-7-ylmethoxy)-piperidine-1-carboxylic acid tert-butyl ester [example 1(c)], and 1.41 g (10.14 mmol, 3.0 equiv.) of 3-bromo-1-propanol in 10 ml of toluene and 0.1 ml of N-methyl-pyrrolidone was treated with 1.44 g (10.14 mmol, 3.0 equiv.) of anhydrous disodium hydrogen phosphate. The suspension was refluxed for 24 h under an inert atmosphere. Subsequently, the reaction mixture was poured into 200 ml of an ice/water mixture and extracted three times with 150 ml of ethyl acetate. The combined organic phases were washed five 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 1:1 mixture of hexane and ethyl acetate as the eluent and yielded 1.94 g (2.87 mmol, 85.2% of theory) of (3R,4R)-3-[1-(3-hydroxy-propyl)-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 yellow oil; MS: 675 (M+H)+.

Provenance & Evidence