2-(3,5-Dichlorophenyl)morpholine → (2S)-3-(2-(3,5-dichlorophenyl)morpholino)-1,1,1-trifluoropropan-2-ol

Participants

Reaction Steps

2-(3,5-Dichlorophenyl)morpholine oxalate (1 g) from Chem-Impex was added to 5% aq NaOH and dichloromethane and extracted (3×100 mL dichloromethane). Combined extracts were dried over Na2SO4, filtered and concentrated to afford 728 mg of 2-(3,5-dichlorophenyl)morpholine as the free-base. In a 100 mL round-bottom flask, 2-(3,5-dichlorophenyl)morpholine (728 mg, 3.14 mmol) and (S)-2-(trifluoromethyl)oxirane (527 mg, 4.7 mmol) were combined with acetonitrile (10.0 ml) to give a yellow solution. Stirring was continued at room temperature for 3 days. Reaction mixture was concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 40 g, 5% to 20% EtOAc in hexanes) to afford (2S)-3-(2-(3,5-dichlorophenyl)morpholino)-1,1,1-trifluoropropan-2-ol (1.06 g, 98%) as a colorless oil. (M+H)+=344, 346 m/e. Used as is.

Provenance & Evidence