反应条件
1.1: hexane; tetrahydrofuran / 1.08 h / 0 - 13 °C / Industry scale; Inert atmosphere
1.2: 2 h / 20 °C / pH 3.88 - 4.28 / Industry scale
2.1: potassium hydroxide / toluene; water / 0.33 h / 12.5 °C / Industry scale; Inert atmosphere
2.2: 1.65 h / 12.5 - 14.6 °C / Industry scale; Inert atmosphere
3.1: (9R)-1-[3,5-bis(trifluoromethyl)benzyl]cinchonan-1-ium-9-ol bromide / toluene; water / 16 h / 10 °C / Industry scale; Inert atmosphere
4.1: toluene / 6.67 h / 90 °C / Industry scale
5.1: hydrogen / palladium 10 on activated carbon / toluene; methanol / 20 - 27 °C / 3102.97 Torr / Industry scale
5.2: 20 °C / pH 6.3 / Industry scale
View Scheme
参考文献
MERCK SHARP and DOHME CORP.; BELYK, Kevin, M.; BULGER, Paul, G.; LINGHU, Xin; MALONEY, Kevin, M.; MCLAUGHLIN, Mark; PAN, Jun; XIANG, Bangping; XU, Yingju; YIN, Jingjun
Patent: WO2011/5731 A2, 2011 ;
WO 2011/005731 A2