tert-Butanol → tert-Butyl (5-methylpyrazin-2-yl)carbamate

Participants

Reaction Conditions

Reaction Steps

To a flask fitted with overhead stirrer, condenser, thermometer and nitrogen line was added 5-methylpyrazine-2-carboxylic acid (1.0 eq), tert-butanol (3.5 vols) and di-isopropylethylamine (1.5 eq) under a nitrogen atmosphere. The mixture was heated to 82° C., then diphenylphosphorylazide (1.0 eq) was added over a time period of 5-14 hours, maintaining the temperature of the reaction mixture at approximately 82° C. The reaction mixture was stirred for at least 1.5 hours, and then cooled to approximately 60° C. A solution of 4% w/w sodium hydroxide (1.75 eq) was added over a period of 2 hours. The mixture was cooled to 15° C. over at least 5 hours then held at 15° C. for 3 hours. The batch was then filtered, and the solid slurry washed with water (2 vols). The batch was again slurry washed with water (2 vols). After drying at 55-60° C. overnight, the desired product was obtained as a solid (corrected yield 56-63%). 1H NMR δ (400 MHz CDCl3): 9.18 (s, 1H), 8.17 (bs, 1H), 8.11 (s, 1H), 2.51 (s, 3H), 1.56 (s, 9H)

Provenance & Evidence