Benzylethanolamine → 4-Benzylmorpholine-2-carbonitrile

Participants

Reaction Conditions

Reaction Steps

A 500 mL reactor under nitrogen was successively loaded with toluene (50 mL) and 2-chloro-2-propenenitrile (14.26 mL, 179 mmol) at 25° C., and then 2-[(phenylmethyl)amino]ethanol (25.4 mL, 179 mmol) was added over 15 minutes. The reaction mixture was post-agitated at 25° C. for 16 hours. The mixture was diluted with toluene (100 mL), cooled to −5° C., and potassium tert-butoxide (20.04 g, 179 mmol) in THF (90 mL) was slowly added over 30 minutes, maintaining the temperature at −5° C. to 0° C. The mixture was post-agitated at about −5° C. to 0° C. for 1 hour, then quenched by the addition of water (150 mL), and the mixture was allowed to warm to 25° C. The aqueous was extracted with EtOAc (4×150 mL), dried (Na2SO4), filtered, and concentrated to afford the title compound (36 g) as a brown solid. LC-MS (ES) m/z=203 [M+H]+.

Provenance & Evidence