Nitrobenzene → 2-(Trifluoromethyl)pyrimidin-5-ol

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-(trifluoromethyl)-1,4,5,6-tetrahydro-5-pyrimidinol (6.50 g, 38.7 mmol) and nitrobenzene (30 mL) was heated to 90° C. to form a homogeneous solution. At this temperature, a solution of sodium methoxide (8.5 g, 157 mmol) in methanol (30 mL) was added portionwise, allowing the methanol to distill off before next addition (the whole process took about 3 h). Then the reaction mixture was heated to 120° C. for 1 h. The reaction mixture was cooled to room temperature, and then partitioned between ethyl acetate and water. The organic phase was separated off. The aqueous phase adjusted to pH 4.0 with 6M aqueous HCl and then extracted with EA. The organic phase was dried over sodium sulfate, and filtered. Concentrated in vacuo then afforded the title compound (533 mg, 3.25 mmol, 8.4% yield). LCMS: rt=1.78 min, [M+H+]=165

Provenance & Evidence