Sodium Hydroxide → Efavirenz

Participants

Reaction Steps

A solution of (1S,4R)-N-(4-chloro-2-((S)-4-cyclopropyl-1,1,1-trifluoro-2-hydroxybut-3-yn-2-yl)phenyl)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxamide (10, 5.0 g, 10.6 mmol), methyl tert-butyl ether (30 mL), 1 N NaOH aqueous (25 mL), and 4-nitrophenyl chloroformate (2.8 g, 13.8 mmol) was stirred at room temperature for 10 minutes. Then two layers were separated and NaOH (2.1 g, 52.5 mmol) was added to the organic layer. The mixture was stirred for 1 hour. The suspension was filtered and rinsed with methyl tert-butyl ether (3×10 mL), then the filtrate was washed with 1 N NaOH (25 mL), water (25 mL), and the two layers were separated. The organic layer was evaporated to about 10 mL, heptanes (25 mL) was added. Then the mixture was stirred at room temperature for an hour, the resulting suspension was filtered and washed with heptanes to give 1.5 g (S)-6-chloro-4-(cyclopropylethynyl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-ben zoxazin-2-one (Efavirenz, 1) as a white or off-white solid.

Provenance & Evidence