反应详情

温度

0 °C

To the product of Example 126A (0.20 g, 1.1 mmol) in 35 mL THF was added Et3N (0.37 mL, 2.7 mmol). This mixture was cooled to 0° C. and 2,3-dichlorobenzoyl chloride (Lancaster, 0.27 g, 1.3 mmol) in 5 mL THF was added dropwise via syringe. This mixture stirred at ambient temperature for 1 hour then was warmed to reflux and was allowed to stir for 3 hours. The mixture was cooled to ambient temperature and was quenched with 5 mL saturated, aqueous NH4Cl and diluted with 10 mL EtOAc. The layers were separated and the aqueous layer was extracted 2×5 mL EtOAc and 2×5 mL CH2Cl2. The combined organics were washed 1×5 mL saturated, aqueous NaCl then were dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure and purified via flash column chromatography (SiO2, 10% CH3OH:EtOAc). The material was still impure so it was purified again via flash column chromatography (SiO2, 1:1 hexanes:EtOAc) to provide the title compound (0.105 g, 0.29 mmol, 27% yield). 1H NMR (300 MHz, CDCl3) δ ppm 2.26 (s, 3H), 2.28 (s, 3H), 3.30 (s, 3H), 3.76 (t, J=4.6 Hz, 2H), 4.40 (t, J=4.2 Hz, 2H), 7.23 (t, J=7.7 Hz, 1H), 7.49 (dd, J=8.0, 1.5 Hz, 1H), 7.72 (dd, J=7.6, 1.5 Hz, 1H); MS (DCI/NH3) m/z 359 (M+H)+; Anal. calculated for C15H16Cl2N2O2S: C, 50.15; H, 4.49; N, 7.80. Found: C, 50.17; H, 4.26; N, 7.69.

1. temperaturethen was warmed
2. temperatureto reflux
3. stirringto stir for 3 hours
4. temperatureThe mixture was cooled to ambient temperature
5. customwas quenched with 5 mL saturated
6. additionaqueous NH4Cl and diluted with 10 mL EtOAc
7. customThe layers were separated
8. extractionthe aqueous layer was extracted 2×5 mL EtOAc and 2×5 mL CH2Cl2
9. washThe combined organics were washed 1×5 mL saturated
10. dry with materialaqueous NaCl then were dried over anhydrous Na2SO4
11. filtrationfiltered
12. concentrationconcentrated under reduced pressure
13. custompurified via flash column chromatography (SiO2, 10% CH3OH:EtOAc)
14. customwas purified again via flash column chromatography (SiO2, 1:1 hexanes:EtOAc)