反应详情

温度

35 °C

[4-(4-Chloro-phenyl)-5-(2,2,2-trifluoro-ethoxy)-pyridin-2-yl]-methanol (17.4 g, 55 mmol) was dissolved in acetonitrile (235 mL). Phosphate buffer (pH 6.7, 220 mL) and 2,2,6,6-tetra-methylpiperidine 1-oxyl radical (TEMPO, 0.6 g) was added and the solution was warmed to 35° C. To this warm solution under argon was added with stirring over 2 h simultaneously a solution of NaOCl2 (12.4 g) in water (58 mL) and NaOCl (0.85 mL, 10% solution) in water (35 mL). Stirring was continued for 20 h at 35° C. after which time the solution was cooled to room temperature and quenched by addition of in sequence water (420 mL), 2 N NaOH solution (65 mL) and Na2SO3 solution (17.1 g in 285 mL water). This mixture was stirred for 30 min and acidified with 2 N HCl (175 mL). The mixture was extracted once with ethyl acetate/THF (800/150 mL), and once with ethyl acetate (500 mL). Organic phases were washed with brine (800 mL), pooled and dried with Na2SO4. The solvent phase was concentrated to a volume of ˜100 mL, n-heptane (150 mL) was added and the solvent phase was concentrated again to ˜100 mL. This was repeated twice. n-Heptane (100 mL) was added. The product precipitated upon stirring, was filtered off and dried to give the title compound as a white solid (18.4 g, quant.), LC-MS (UV peak area/ESI) ˜100%, 332.029 (M+H)+.

1. additionTo this warm solution under argon was added
2. temperatureafter which time the solution was cooled to room temperature
3. customquenched by addition of in sequence water (420 mL), 2 N NaOH solution (65 mL) and Na2SO3 solution (17.1 g in 285 mL water)
4. stirringThis mixture was stirred for 30 min
5. extractionThe mixture was extracted once with ethyl acetate/THF (800/150 mL)
6. washOrganic phases were washed with brine (800 mL)
7. dry with materialdried with Na2SO4
8. concentrationThe solvent phase was concentrated to a volume of ˜100 mL, n-heptane (150 mL)
9. additionwas added
10. concentrationthe solvent phase was concentrated again to ˜100 mL
11. additionn-Heptane (100 mL) was added
12. customThe product precipitated
13. stirringupon stirring
14. filtrationwas filtered off
15. customdried