5-Chloropyrazinoic acid → tert-Butyl 5-chloropyrazine-2-carboxylate

Participants

Reaction Conditions

Reaction Steps

A solution of 5-chloro-pyrazine-2-carboxylic acid (10.00 g, 63.07 mmol) in tetrahydrofuran (126 mL) was treated with a solution of tert-butyl 2,2,2-trichloroacetimidate (23 mL, 126.14 mmol) in cyclohexane (126 mL). The reaction was stirred at 25° C. for 5 min and then was treated with boron trifluoride dimethyl etherate (3.2 mL, 25.23 mmol). The resulting reaction mixture was stirred at 25° C. for 16 h and then was diluted with ethyl acetate (200 mL), washed with a saturated aqueous sodium bicarbonate solution (200 mL) and water (200 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 65M, Silica, 1/9 ethyl acetate/hexanes) afforded 5-chloro-pyrazine-2-carboxylic acid tert-butyl ester (12.73 g, 94%) as a colorless oil: EI-HRMS m/e calcd for C9H11ClN2O2 (M+) 214.0502, found 214.0510.

Provenance & Evidence