反应详情

温度

40 °C

To a solution of Example 81C (0.45 g, 1.1 mmol) and N-(tert-butyl)hydroxylamine hydrochloride (0.28 g, 2.3 mmol) in THF (20 mL) was added potassium tert-butoxide (0.19 g, 1.7 mmol). The mixture was warmed to 40° C. and stirred for 18 hours then additional potassium tert-butoxide was added (0.40 g). The mixture was stirred for an additional 1 hour then partitioned between saturated aqueous NaHCO3 (10 mL) and EtOAc (10 mL). The layers were separated and the aqueous phase was extracted with EtOAc (3×10 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated. Purification by column chromatography (SiO2, 50% hexanes/EtOAc then 100% EtOAc then 9:1:0.1 EtOAc:MeOH:Et3N) afforded the title compound (0.41 g, 0.88 mmol, 78% yield). 1H NMR (300 MHz, CDCl3) δ ppm 0.96 (t, J=7.3 Hz, 3H) 1.20 (s, 9H) 1.34-1.43 (m, 2H) 1.42 (s, 9H) 1.64-1.72 (m, 2H) 3.72 (s, 3H) 4.27 (dd, J=7.5 Hz, 2H) 5.75 (s, 1H) 7.01 (s, 1H) 7.46 (dd, J=8.6, 1.9 Hz, 1H) 7.67 (d, J=8.8 Hz, 1H) 8.10 (d, J=2.0 Hz, 1H); MS (DCI/NH3) m/z 469 (M+H)+; Anal. calculated for C24H35F3N4O2: Calc: C, 61.52; H, 7.53; N, 11.96. Found: C, 61.18; H, 7.26; N, 11.92.

1. stirringThe mixture was stirred for an additional 1 hour
2. customthen partitioned between saturated aqueous NaHCO3 (10 mL) and EtOAc (10 mL)
3. customThe layers were separated
4. extractionthe aqueous phase was extracted with EtOAc (3×10 mL)
5. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customPurification by column chromatography (SiO2, 50% hexanes/EtOAc