Triethylamine → Dibenzyl-{(1S,2R)-2-benzyloxy-1-(3,5-difluorobenzyl)-2-[(3R,5S,6S)-6-(1-fluorocyclohexylmethoxy)-5-methylmorpholin-3-yl]-ethyl}-amine

Participants

Reaction Conditions

Reaction Steps

Add triphosgene (246 mg, 0.79 mmol) at room temperature to a solution of (3S,5R)-5-[(1R,2S)-1-benzyloxy-2-dibenzylamino-3-(3,5-difluorophenyl)-propyl]-3-methylmorpholin-2-ol (1 g, 1.75 mmol) and triethylamine (0.99 mL, 7 mmol) in anhydrous dichloromethane (17 mL). Stir for 30 min, cool to 0° C. and add (1-fluorocyclohexyl)-methanol (1.16 g, 8.75 mmol) and trimethylsilyl trifluoromethanesulfonate (TMSOTf) (0.64 mL, 3.5 mmol). Stir at 0° C. for 1 hour and at room temperature for 2 hours. Add more trimethylsilyl trifluoromethanesulfonate (0.16 mL, 0.87 mmol) and stir at room temperature for 30 min. Add 10% aqueous potassium carbonate, separate the organic layer and extract the aqueous layer with dichloromethane. Combine the organic layers, dry (sodium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 0:100 to 20:80 hexanes:ethyl acetate), to give the title compound as a colorless oil (375 mg).

Provenance & Evidence