Trifluoroacetic acid → (+/-)-3-amino-5-((3R,4R)-3-((tert-butyldimethylsilyl)oxy)-4-morpholinopiperidin-1-yl)-4-chlorobenzonitrile

Participants

Reaction Steps

(+/−)-tert-butyl (3-((3R,4R)-3-((tert-butyldimethylsilyl)oxy)-4-morpholinopiperidin-1-yl)-2-chloro-5-cyanophenyl)carbamate (138 mg, 0.250 mmol) was treated with TFA (25% in 1,2-dichloroethane, 3 mL, 9.73 mmol) at room temperature for 1 h. The reaction mixture was diluted with dichloromethane and washed with cold saturated sodium bicarbonate/1N aqueous sodium hydroxide (pH 10). The layers were separated and aqueous layer was extracted with dichloromethane two more times. The combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo, the crude product was purified by flash chromatography on silica gel using an automated ISCO system (24 g column, eluting with 5-40% ethyl acetate/hexanes). (+/−)-3-amino-5-((3R,4R)-3-((tert-butyldimethylsilyl)oxy)-4-morpholinopiperidin-1-yl)-4-chlorobenzonitrile (106 mg) was obtained as a yellow/brown solid.

Provenance & Evidence