Acetic Acid → rel-(3S,4S)-4-[(S)-1-(2,4-dimethoxy-benzylamino)-1-(2-fluoro-phenyl)-ethyl]-tetrahydro-furan-3-ol

Participants

Reaction Conditions

Reaction Steps

Under an atmosphere of argon, a solution of rel-(S)-1-[(3S,4S)-4-(tert-butyl-dimethyl-silanyloxy)-tetrahydro-furan-3-yl]-1-(2-fluoro-phenyl)-ethylamine (8.13 g, 23.9 mmol) in 1,2-dichloroethane (80 ml) was treated with 2,4-dimethoxybenzaldehyde (3.98 g, 23.9 mmol), sodium triacetoxyborohydride (10.2 g, 47.9 mmol) and acetic acid (1.37 ml, 23.9 mmol). The reaction mixture was stirred overnight. In order to complete the reaction, 2,4-dimethoxybenzaldehyde (1.99 g, 12.0 mmol) and sodium triacetoxyborohydride (5.08 g, 23.9 mmol) were added and the mixture was stirred overnight. Thereafter, the reaction mixture was cooled to 0° C. and tetrabutylammonium fluoride trihydrate (7.56 g, 23.9 mmol) was added. The mixture was allowed to reach room temperature while stirring for 4 hours. In order to complete the reaction, tetrabutylammonium fluoride trihydrate (2.27 g, 7.18 mmol) was added again, and stirring continued for 4 days. For the workup, the reaction mixture was extracted twice with a mixture of a saturated solution of sodium hydrogencarbonate and dichloromethane. The combined organic layers were dried over sodium sulphate and evaporated. The residue was purified by flash chromatography on silica gel using a gradient of heptane and ethyl acetate=100:0 to 50:50 as the eluent. The rel-(3S,4S)-4-[(S)-1-(2,4-dimethoxy-benzylamino)-1-(2-fluoro-phenyl)-ethyl]-tetrahydro-furan-3-ol (6.8 g, 76% yield) was obtained as a colorless amorphous material.

Provenance & Evidence