Triethylamine → Efavirenz

Temperature

7.5 °C

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, 30 g, 63.9 mmol), dichloromethane (150 mL) and triethylamine (7.11 g, 70.2 mmol) was stirred at 0-5° C. for 20 minutes, then 1-chloroethyl chloroformate (10.0 g, 70.2 mmol) was added dropwise. The mixture was stirred at 5-10° C. for 1 hour. Then N,N-dimethylformamide (150 mL) was added and further evaporated to 220 mL, then K2CO3 (13.3 g, 95.8 mmol) was added. The reaction mixture was stirred at room temperature overnight. Methyl t-butyl ether (300 mL) and water (200 mL) were added to the mixture, and the resulting layers were separated. The organic layer was washed with brine, and concentrated to 60 mL whereupon petroleum ether (200 mL) was added and stirred. The resulting precipitate was filtered and rinsed with petroleum ether to provide 18.4 g (S)-6-chloro-4-(cyclopropylethynyl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-ben zoxazin-2-one (Efavirenz, 1) as an off-white solid.

1. customfurther evaporated to 220 mL
2. stirringThe reaction mixture was stirred at room temperature overnight
3. customthe resulting layers were separated
4. washThe organic layer was washed with brine
5. concentrationconcentrated to 60 mL whereupon petroleum ether (200 mL)
6. additionwas added
7. stirringstirred
8. filtrationThe resulting precipitate was filtered
9. washrinsed with petroleum ether

ORD record

ord-b070086009c24672ba3dabccfe8e3f4b

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08080655B2