1.1: sulfuric acid / dichloromethane / 2.15 h / 10 - 35 °C 2.1: lithium tri-t-butoxyaluminum hydride / tetrahydrofuran / 2 h / -45 - -40 °C / Inert atmosphere 3.1: potassium tert-butylate / tetrahydrofuran / 1.33 h / 25 - 35 °C / Inert atmosphere 3.2: 3 - 5 h / 25 - 35 °C / Inert atmosphere 3.3: Cooling 4.1: triethylamine / 4-(N,N-dimethlyamino)pyridine / tert-butyl methyl ether / 2 h / 25 - 35 °C / Inert atmosphere 5.1: ethylaluminum dichloride / dichloromethane; toluene / 20 h / 0 - 35 °C / Inert atmosphere 5.2: Cooling 6.1: hydrogen / palladium on activated charcoal / ethyl acetate / 16 h / 25 - 35 °C / 3620.13 Torr 7.1: tert.-butylhydroperoxide; sodium hypochlorite / ethyl acetate; water / 7 h / 0 - 5 °C 8.1: potassium carbonate; hydrogen / palladium on activated charcoal / dichloromethane / 24 h / 20 °C 9.1: hydrogen / palladium 10 on activated carbon / ethyl acetate / 16 h / 45 - 50 °C / 2585.81 Torr 10.1: lithium tri-t-butoxyaluminum hydride / tetrahydrofuran / 5 h / 0 - 10 °C 10.2: 0 - 5 °C 11.1: sodium hydroxide; water / tetrahydrofuran; methanol / 4 h / 25 - 35 °C 11.2: pH 1 - 2 View Scheme
参考文献
KYTHERA BIOPHARMACEUTICALS, INC.; MORIARTY, Robert M.; PRASAD, Achampeta Rathan; REID, John Gregory; SWARINGEN Jr., Roy A.
Patent: WO2011/75701 A2, 2011 ;
With sulfuric acid in dichloromethane T=10 - 35°C; 2.15 h; Product distribution / selectivity; Show Experimental Procedure
参考文献
KYTHERA BIOPHARMACEUTICALS, INC.; MORIARTY, Robert M.; PRASAD, Achampeta Rathan; REID, John Gregory; SWARINGEN Jr., Roy A. Patent: WO2011/75701 A2, 2011 ; Location in patent: Page/Page column 77-78, 103-104, 125-126 ;
Multi-step reaction with 3 steps 1.1: sulfuric acid / dichloromethane / 2.15 h / 10 - 35 °C2.1: lithium tri-t-butoxyaluminum hydride / tetrahydrofuran / 2 h / -45 - -40 °C / Inert atmosphere3.1: potassium tert-butylate / tetrahydrofuran / 1.33 h / 25 - 35 °C / Inert atmosphere3.2: 3 - 5 h / 25 - 35 °C / Inert atmosphere3.3: Cooling
参考文献
KYTHERA BIOPHARMACEUTICALS, INC.; MORIARTY, Robert M.; PRASAD, Achampeta Rathan; REID, John Gregory; SWARINGEN Jr., Roy A. Patent: WO2011/75701 A2, 2011 ;
Multi-step reaction with 5 steps 1.1: sulfuric acid / dichloromethane / 2.15 h / 10 - 35 °C2.1: lithium tri-t-butoxyaluminum hydride / tetrahydrofuran / 2 h / -45 - -40 °C / Inert atmosphere3.1: potassium tert-butylate / tetrahydrofuran / 1.33 h / 25 - 35 °C / Inert atmosphere3.2: 3 - 5 h / 25 - 35 °C / Inert atmosphere3.3: Cooling4.1: triethylamine / 4-(N,N-dimethlyamino)pyridine / tert-butyl methyl ether / 2 h / 25 - 35 °C / Inert atmosphere5.1: ethylaluminum dichloride / dichloromethane; toluene / 0.25 h / 0 °C / Inert atmosphere5.2: 18.33 h / 0 - 25 °C / Inert atmosphere5.3: 0 °C
参考文献
KYTHERA BIOPHARMACEUTICALS, INC.; MORIARTY, Robert M.; PRASAD, Achampeta Rathan; REID, John Gregory; SWARINGEN Jr., Roy A. Patent: WO2011/75701 A2, 2011 ;
Multi-step reaction with 5 steps 1.1: sulfuric acid / dichloromethane / 2.15 h / 10 - 35 °C2.1: lithium tri-t-butoxyaluminum hydride / tetrahydrofuran / 2 h / -45 - -40 °C / Inert atmosphere3.1: potassium tert-butylate / tetrahydrofuran / 1.33 h / 25 - 35 °C / Inert atmosphere3.2: 3 - 5 h / 25 - 35 °C / Inert atmosphere3.3: Cooling4.1: triethylamine / 4-(N,N-dimethlyamino)pyridine / tert-butyl methyl ether / 2 h / 25 - 35 °C / Inert atmosphere5.1: ethylaluminum dichloride / dichloromethane; toluene / 20 h / 0 - 35 °C / Inert atmosphere5.2: Cooling
参考文献
KYTHERA BIOPHARMACEUTICALS, INC.; MORIARTY, Robert M.; PRASAD, Achampeta Rathan; REID, John Gregory; SWARINGEN Jr., Roy A. Patent: WO2011/75701 A2, 2011 ;
