反应详情

温度

45 °C

Charge a flask with (S)-α,α-diphenyl-2-pyrrolidinemethanol (253 mg, 1.0 mmol) and purge flask with nitrogen. Dilute with 1M borane in THF (43 mL, 43 mmol) and heat to 45° C. under nitrogen. Dissolve methanesulfonic acid 6-(3,5-difluoro-2-methylsulfanyl-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl ester (6.5 g, 10.6 mmol) in THF (40 mL) and add to the catalyst solution via syringe pump over 2 hours. After complete addition, add ethanolamine (12.8 mL, 212 mmol) slowly and heat at 45° C. for 3 hours. Cool the reaction to room temperature and pour into saturated aqueous ammonium chloride. Extract with methylene chloride, dry over sodium sulfate, filter and concentrate. Purify over silica gel eluting with 3% methanol in methylene chloride to yield 7.4 g (93%) of the title compound (60:40 mixture of diastereomers). LCMS Rt (0.01% heptafluorobutyric acid:1.0% isopropylalcohol:water is mobile phase A and 0.01% heptafluorobutyric acid:1.0% isopropylalcohol:acetonitrile is mobile phase B; gradient method 25 to 95% B, Purity@254 nm)=2.91 and 2.94 mm (100%); mass spectrum (ion spray): m/z=614.2 (M+H).

1. custompurge flask with nitrogen
2. additionAfter complete addition
3. temperatureheat at 45° C. for 3 hours
4. temperatureCool
5. customthe reaction to room temperature
6. extractionExtract with methylene chloride
7. dry with materialdry over sodium sulfate
8. filtrationfilter
9. concentrationconcentrate
10. customPurify over silica gel eluting with 3% methanol in methylene chloride