Benzylethanolamine → 4-Benzylmorpholine-2-carbonitrile

Temperature

25 °C

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]+.

1. temperaturecooled to −5° C.
2. temperaturemaintaining the temperature at −5° C. to 0° C
3. stirringThe mixture was post-agitated at about −5° C. to 0° C. for 1 hour
4. customquenched by the addition of water (150 mL)
5. temperatureto warm to 25° C
6. extractionThe aqueous was extracted with EtOAc (4×150 mL)
7. dry with materialdried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated

ORD record

ord-8517dbd472c24d619d0b83556e3c57ad

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08697685B2