反应详情

To the product of Example 126A (0.20 g, 1.1 mmol) in 30 mL THF was added Et3N (0.37 mL, 2.7 mmol) followed by 2,2-difluoro-1,3-benzodioxole-4-carbonyl chloride (Lancaster, 0.29 g, 1.3 mmol). This mixture was stirred at ambient temperature for 17 hours then was warmed to reflux and allowed to stir for an additional 4 hours. The mixture was then cooled to ambient temperature and additional 2,2-difluoro-1,3-benzodioxole-4-carbonyl chloride (73 mg, 0.33 mmol) and Et3N (0.37 mL, 2.7 mmol) were added. This mixture was warmed to reflux at which temperature it stirred for 2 hours. The mixture was then cooled to ambient temperature, diluted with 10 mL EtOAc and washed with 5 mL saturated, aqueous NH4Cl. The layers were separated and the aqueous layer was extracted 2×5 mL EtOAc. The combined organics were dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure and purified via flash column chromatography (SiO2, 50% hexanes:EtOAc) to afford the title compound (0.22 g, 0.59 mmol, 55% yield). 1H NMR (300 MHz, CDCl3) δ ppm 2.26 (s, 3H), 2.28 (s, 3H), 3.32 (s, 3H), 3.83 (t, J=5.1 Hz, 2H), 4.44 (t, J=5.1 Hz, 2H), 7.12 (d, J=4.4 Hz, 1H), 7.14 (s, 1H), 7.89 (dd, J=6.6, 2.9 Hz, 1H); MS (DCI/NH3) m/z 371 (M+H)+; Anal. calculated for C16H16F2N2O4S: C, 51.89; H, 4.35; N, 7.56. Found: C, 52.27; H, 4.24; N, 7.53.

1. temperaturethen was warmed
2. temperatureto reflux
3. stirringto stir for an additional 4 hours
4. temperatureThe mixture was then cooled to ambient temperature
5. temperatureThis mixture was warmed
6. temperatureto reflux at which temperature it
7. stirringstirred for 2 hours
8. temperatureThe mixture was then cooled to ambient temperature
9. washwashed with 5 mL saturated
10. customThe layers were separated
11. extractionthe aqueous layer was extracted 2×5 mL EtOAc
12. dry with materialThe combined organics were dried over anhydrous Na2SO4
13. filtrationfiltered
14. concentrationconcentrated under reduced pressure
15. custompurified via flash column chromatography (SiO2, 50% hexanes:EtOAc)