反应详情

温度

80 °C

To a suspension of 60% NaH (577 mg, 14.4 mmol) in DMF (15 mL) at 0° C. was added thiophenol (1.47 mL, 14.4 mmol) and the resultant mixture was warmed to room temperature and stirred for 1.5 h. To this mixture was added the 3-Bromo-2-methyl-pyridine 1-oxide (900 mg, 4.79 mmol) and the resultant yellow solution was heated to 80° C. for 96 h. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was treated with EtOAc (100 mL), washed with brine (4×50 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. Purification by flash chromatography on silica gel (EtOAc/MeOH, 100:0 then 95:5) gave a mixture of 2-methyl-3-phenylsulfanyl-pyridine 1-oxide and a di-substituted thiophenol by-product. The mixture was treated with Ac2O (3 mL) and heated at 80° C. overnight. The mixture was cooled to room temperature, diluted with CH2Cl2 (40 mL), H2O (10 mL) and saturated aqueous NaHCO3 (40 mL). The aqueous phase was separated and extracted with CH2Cl2 (2×20 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated. Purification by flash chromatography on silica gel (Hexanes/EtOAc, 70:30) gave Acetic acid 3-phenylsulfanyl-pyridin-2-ylmethyl ester (259 mg, 25% over 2 steps) as a yellow oil. 1H NMR (CDCl3) δ 2.11 (s, 3H), 5.37 (s, 2H), 7.18 (dd, 1H, J=7.9, 4.9 Hz), 7.27-7.38 (m, 5H), 7.53 (dd, 1H, J=7.9, 1.7 Hz), 8.50 (dd, 1H, J=4.7, 1.8 Hz).

1. temperatureThe reaction mixture was cooled to room temperature
2. concentrationconcentrated under reduced pressure
3. additionThe residue was treated with EtOAc (100 mL)
4. washwashed with brine (4×50 mL)
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customPurification by flash chromatography on silica gel (EtOAc/MeOH, 100:0
9. custom95:5) gave
10. temperatureheated at 80° C. overnight
11. temperatureThe mixture was cooled to room temperature
12. customThe aqueous phase was separated
13. extractionextracted with CH2Cl2 (2×20 mL)
14. dry with materialThe combined organic extracts were dried (Na2SO4)
15. filtrationfiltered
16. concentrationconcentrated
17. customPurification by flash chromatography on silica gel (Hexanes/EtOAc, 70:30)