Hydrogen Bromide → 2-Bromo-3-[2-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]-5-pyridyl]propionitrile

Participants

Reaction Conditions

Reaction Steps

To a mixture of 5-amino-2-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]pyridine (9.1 g), an aqueous solution of HBr (47%, 14.2 ml) and acetone (150 ml) was added dropwise, at temperature not exceeding 10° C. a solution of sodium nitrite (NaNO2) (2.33 g) in water (10 ml). The mixture was stirred for 30 minutes at 10° C., to which was added acrylonitrile (CH2 =CHCN) (12.1 ml). To the mixture was added, while stirring vigorously, copper(I) oxide (Cu2O) (0.1 g). The reaction mixture was stirred for further one hour at temperature ranging from 30° to 35° C., followed by concentration under reduced pressure. The concentrate was poured into water, which was made alkaline with a conc. ammonia water, followed by extraction with ethyl acetate. The ethyl acetate layer was washed with water and dried (MgSO4), then the solvent was distilled off under reduced pressure. The residual oily product was subjected to a silica gel column chromatography. From the fractions eluted with ethyl acetate--hexane (1:1, v/v), was obtained 2-bromo-3-[2-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]-5-pyridyl]propionitrile (6.11 g, 48%), which was recrystallized from ethyl acetate--hexane to give colorless crystals, m.p.93°-94° C.

Provenance & Evidence