Triethylamine → Rac-Efavirenz

Participants

Reaction Conditions

Reaction Steps

A solution of N-(4-chloro-2-(4-cyclopropyl-1,1,1-trifluoro-2-hydroxybut-3-yn-2-yl)phenyl)acetamide (5, R1 is methyl, 1.1 g, 3.3 mmol), toluene (5.5 mL) and triethylamine (0.5 mL, 3.65 mmol) was stirred at 0-5° C. under nitrogen then 1-chloroethyl chloroformate (0.52 g, 3.65 mmol) was added dropwise. The mixture was stirred at 5-10° C. overnight. Water (20 mL) was added and the mixture was separated. The organic layer was evaporated to dryness whereupon N,N-dimethyl formamide (5 mL) and K2CO3 (0.9 g, 6.6 mmol) were added. The reaction mixture was stirred at room temperature for 1 day. Toluene (20 mL) and water (20 mL) were added to the mixture, and the resulting mixture was separated. The organic layer was washed with water (20 mL), and evaporated to dryness to give 6-chloro-4-(cyclopropylethynyl)-4-(trifluoromethyl)-1H-benzo[d][1,3]oxazin-2(4H)-one as an off-white solid. 1H NMR (CDCl3) δ 9.64 (s, 1H), 7.49 (a, s, 1H), 7.36 (dd, J=8.4, 1.8 Hz, 1H), 6.87 (d, J=8.4 Hz, 1H), 1.43-1.36 (m, 1H), 0.97-0.91 (m, 2H), 0.88-0.86 (m, 2H),

Provenance & Evidence