Sodium Hydroxide → Efavirenz

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-benzoxazin-2-one (Efavirenz, 1) as a white or off-white solid.

1. customThen two layers were separated
2. filtrationThe suspension was filtered
3. washrinsed with methyl tert-butyl ether (3×10 mL)
4. washthe filtrate was washed with 1 N NaOH (25 mL), water (25 mL)
5. customthe two layers were separated
6. customThe organic layer was evaporated to about 10 mL, heptanes (25 mL)
7. additionwas added
8. stirringThen the mixture was stirred at room temperature for an hour
9. filtrationthe resulting suspension was filtered
10. washwashed with heptanes

ORDレコード

ord-3accfee2044d43beb9fc0f5032614429

出典データセット

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08378143B2