Hydrochloric Acid → HCID 69672521, compound

Participants

Reaction Conditions

Reaction Steps

A solution of ethyl 6-isopropyl-2-(trifluoromethyl)pyrimidine-4-carboxylate (2.00 g, 7.63 mmol, from Step A) in tetrahydrofuran (40 mL) was added to 1.0M potassium tert-butoxide in THF (22.9 mL, 22.9 mmol) held at −40° C. After stirring for 45 minutes at this temperature, oxygen was introduced below the surface of the reaction solution via a syringe attached to a balloon containing oxygen. The oxygen was bubbled subsurface periodically (by addition and removal of an outlet) for 20 minutes, while maintaining the reaction temperature between −40 to −30° C. The reaction was then allowed to slowly reach room temperature with periodic bubbling of oxygen through the solution. Near a temperature of −30 deg C., the reaction turned from purple to orange in color. The reaction was kept under atmosphere of oxygen overnight, at which time the reaction was quenched with water and sodium sulfite (2 g, 20 mmol) was added. Lithium hydroxide, monohydrate (0.928 g, 22.1 mmol) was also added and the reaction was stirred overnight. Concentrated HCl was added drop wise into the reaction to achieve pH between 3 and 4. The layers were separated and the THF layer was reserved for addition to the subsequent two ethyl acetate extractions. The combined extracts were washed with brine, dried over sodium sulfate, filtered and concentrated, then azeotroped twice with MeOH to afford a yellow syrup which was used without further purification (1.7 g, 62%). 1H NMR (400 MHz, CD3OD) δ 8.51 (s, 1H), 1.57 (s, 6H); LCMS (M+H)+: 251.0

Provenance & Evidence