Ethanolamine → Methanesulfonic acid 6-(3,5-difluoro-2-methylsulfanyl-phenyl)-5-{hydroxy-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methyl}-naphthalen-2-yl ester

関与物質

反応条件

反応手順

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).

情報源と証拠