N-Methoxy-N-methylacetamide → HCID 9856131, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 4-(3-bromo-4-fluorobenzyl)morpholine (35.5 g) of Preparation No. 53 in THF (400 mL) is cooled to −75° C., and n-butyllithium is added via addition funnel maintaining the temperature below −65° C. A solution of N-methyl-N-methoxyacetamide (16.0 g, prepared as described in Tetrahedron Lett. 1983, 24, 1857) in THF (50 mL) is added via addition funnel, again maintaining temperature below −65° C. The reaction is stirred at −75° C. for 1 hour and then is allowed to warm to room temperature overnight. The reaction mixture is quenched with 1 N HCl (150 mL) and diluted with ethyl acetate (400 mL). The layers are separated, and the aqueous layer is basified with sat. sodium bicarbonate solution. The aqueous layer is extracted with ethyl acetate (2×100 mL). The combined organic layers are washed with sat. sodium bicarbonate (2×100 mL) and brine (50 mL). The aqueous layers are back-extracted with ethyl acetate (100 mL). The combined organic layers are dried (Na2SO4) and concentrated in vacuo to a yellow oil. The oil is purified by fractional distillation at 135-140° C./0.3 torr to afford 19.7 g (64%) of the title compound as a clear, colorless oil.

Provenance & Evidence