1-(2,2-二氟苯并二氧代-5-基)环丙烷甲腈合成路线 （共 11 条）
反应条件
1: With sodium hydroxide in ethanol T=77 - 80°C; 16 h; 2: With hydrogenchloride in ethanol; dichloromethane T=10 - 25°C;
参考文献
VERTEX PHARMACEUTICALS INCORPORATED; ALARGOVA, Rossitza Gueorguieva; DUNBAR, Craig Antony; KADIYALA, Irina Nikolaevna
Patent: WO2014/14841 A1, 2014 ;
Location in patent: Paragraph 00314 - 00317 ;
反应条件
hydrogenchloride; NaOH in ethanol
参考文献
VERTEX PHARMACEUTICALS INCORPORATED
Patent: US2012/46330 A1, 2012 ;
US 20120046330 A1
反应条件
1: sodium hydroxide; water / ethanol / 80 °C 2: thionyl chloride / toluene / 0.5 h / 60 °C 3: triethylamine; 4-(N,N-dimethlyamino)pyridine / toluene / 2 h 4: hydrogenchloride; water / acetonitrile / 40 - 45 °C View Scheme
参考文献
VERTEX PHARMACEUTICALS INCORPORATED; VERWIJS, Marinus, Jacobus; KARKARE, Radhika; MOORE, Michael, Douglas
Patent: WO2014/71122 A1, 2014 ;
反应条件
tetra-n-octylammonium bromide; potassium hydroxide in water
T=70°C; 1 h;
参考文献
VERTEX PHARMACEUTICALS INCORPORATED; YOUNG, Christopher
Patent: WO2010/37066 A2, 2010 ;
Location in patent: Page/Page column 12; 26 ;
反应条件
1.1: sodium salt of phosphorous acid; tri-tert-butyl phosphine / bis(dibenzylideneacetone)-palladium(0) / toluene; hexanes / 0.83 h / 23 °C / Inert atmosphere
1.2: 70 °C
2.1: hydrogenchloride / water; dimethyl sulfoxide / 40 - 75 °C
3.1: tetra-n-octylammonium bromide; potassium hydroxide / water / 1 h / 70 °C
View Scheme
参考文献
VERTEX PHARMACEUTICALS INCORPORATED; KESHAVARZ-SHOKRI, Ali; ZHANG, Beili; ALCACIO, Tim, Edward; LEE, Elaine, Chungmin; ZHANG, Yuegang; KRAWIEC, Mariusz
Patent: WO2011/119984 A1, 2011 ;
WO 2011/119984 A1
反应条件
1.1: sodium bis(2-methoxyethoxy)aluminium dihydride / toluene / 15 - 40 °C
1.2: 0.5 h / 40 - 50 °C
2.1: thionyl chloride / 4-(N,N-dimethlyamino)pyridine / tert-butyl methyl ether / 1.5 h / 15 - 30 °C
3.1: dimethyl sulfoxide / 1 h / 30 - 40 °C
4.1: tetra-n-octylammonium bromide; potassium hydroxide / water / 1 h / 70 °C
View Scheme
参考文献
VERTEX PHARMACEUTICALS INCORPORATED; KESHAVARZ-SHOKRI, Ali; ZHANG, Beili; ALCACIO, Tim, Edward; LEE, Elaine, Chungmin; ZHANG, Yuegang; KRAWIEC, Mariusz
Patent: WO2011/119984 A1, 2011 ;
WO 2011/119984 A1
反应条件
1: thionyl chloride / 4-(N,N-dimethlyamino)pyridine / tert-butyl methyl ether / 1.5 h / 15 - 30 °C
2: dimethyl sulfoxide / 1 h / 30 - 40 °C
3: tetra-n-octylammonium bromide; potassium hydroxide / water / 1 h / 70 °C
View Scheme
参考文献
VERTEX PHARMACEUTICALS INCORPORATED; KESHAVARZ-SHOKRI, Ali; ZHANG, Beili; ALCACIO, Tim, Edward; LEE, Elaine, Chungmin; ZHANG, Yuegang; KRAWIEC, Mariusz
Patent: WO2011/119984 A1, 2011 ;
WO 2011/119984 A1
参考文献
Vertex Pharmaceuticals Incorported
Patent: US2011/98311 A1, 2011 ;
反应条件
1: dimethyl sulfoxide / 1 h / 30 - 40 °C
2: tetra-n-octylammonium bromide; potassium hydroxide / water / 1 h / 70 °C
View Scheme
参考文献
VERTEX PHARMACEUTICALS INCORPORATED; KESHAVARZ-SHOKRI, Ali; ZHANG, Beili; ALCACIO, Tim, Edward; LEE, Elaine, Chungmin; ZHANG, Yuegang; KRAWIEC, Mariusz
Patent: WO2011/119984 A1, 2011 ;
WO 2011/119984 A1
反应条件
1: hydrogenchloride / water; dimethyl sulfoxide / 40 - 75 °C
2: tetra-n-octylammonium bromide; potassium hydroxide / water / 1 h / 70 °C
View Scheme
参考文献
VERTEX PHARMACEUTICALS INCORPORATED; KESHAVARZ-SHOKRI, Ali; ZHANG, Beili; ALCACIO, Tim, Edward; LEE, Elaine, Chungmin; ZHANG, Yuegang; KRAWIEC, Mariusz
Patent: WO2011/119984 A1, 2011 ;
WO 2011/119984 A1
