2,2-二氟-1,3-苯并二噁茂-5-羧酸合成路线 （共 12 条）
反应条件
1: With sodium hydroxide in methanol T=20°C; 2: With hydrogenchloride in water pH=3;
参考文献
BIOENERGENIX
Patent: US2012/277224 A1, 2012 ;
Location in patent: Page/Page column 26 ;
US 20120277224 A1
反应条件
1: With hydrogen fluoride; boron trifluoride T=0°C; 1 h; 2: 2,2-difluoro-1,3-benzodioxole T=0 - 55°C; 17.5 h; 3: With potassium hydroxide; sulfuric acid; water more than 3 stages;
参考文献
Pleschke, Axel; Marhold, Albrecht
Patent: US2005/277692 A1, 2005 ;
Location in patent: Page/Page column 3 ;
反应条件
1.1: triethylamine / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 24 h / 100 °C 2.1: sodium hydroxide / methanol / 20 °C 2.2: pH 3 View Scheme
参考文献
US2012/277224 A1, ;
US 20120277224 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 5.1: sodium hydroxide; water / ethanol / 80 °C View Scheme
参考文献
VERTEX PHARMACEUTICALS INCORPORATED
Patent: US2012/46330 A1, 2012 ;
US 20120046330 A1
反应条件
in diethyl ether T=-78 - 20°C;
参考文献
Wang, Aihua; Prouty, Catherine P.; Pelton, Patricia D.; Yong, Maria; Demarest, Keith T.; Murray, William V.; Kuo, Gee-Hong
Bioorganic and Medicinal Chemistry Letters, 2010 , vol. 20, # 4 p. 1432 - 1435
反应条件
oxalyl dichloride; N,N-dimethyl-formamide in dichloromethane T=20°C; 8 h;
参考文献
VICURON PHARMACEUTICALS INC.
Patent: US2006/211603 A1, 2006 ;
Location in patent: Page/Page column 66 ;
反应条件
1.1: Vitride® / toluene / 2 h / 15 - 40 °C 1.2: 0.5 h / 40 - 50 °C 2.1: 4-(N,N-dimethlyamino)pyridine; thionyl chloride / tert-butyl methyl ether / 1 h / 15 - 30 °C 3.1: dimethyl sulfoxide / 1 h / 30 - 40 °C 3.2: 0.5 h 4.1: potassium hydroxide; tetra-n-octylammonium bromide / water / 1 h / 70 °C 5.1: sodium hydroxide; water / ethanol / 80 °C 6.1: thionyl chloride / toluene / 0.5 h / 60 °C 7.1: triethylamine; 4-(N,N-dimethlyamino)pyridine / toluene / 2 h 8.1: 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
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
5.1: sodium hydroxide; water / ethanol / 80 °C
6.1: thionyl chloride / toluene / 60 °C
7.1: triethylamine / dichloromethane / 0 - 20 °C
8.1: hydrogen / 5 palladium on charcoal / tetrahydrofuran / 96 h / 50 °C / 2250.23 - 3000.3 Torr / autoclave; Inert atmosphere
View Scheme
参考文献
VERTEX PHARMACEUTICALS INCORPORATED; LOOKER, ADAM; Littler, Benjamin Joseph; Choudhury, Anusuya; Harrison, Cristian; Veluri, Ravikanth; Ryan, Michael P.; Jiang, Licong; Luss-Lusis, Eduard
Patent: US2013/116238 A1, 2013 ;
反应条件
1: With sodium bis(2-methoxyethoxy)aluminium dihydride in toluene
T=15 - 40°C;
2: With sodium hydroxide in water; toluene
T=40 - 50°C;
参考文献
VERTEX PHARMACEUTICALS INCORPORATED
Patent: WO2009/73757 A1, 2009 ;
Location in patent: Page/Page column 20 ;
参考文献
Vertex Pharmaceuticals Incorported
Patent: US2011/98311 A1, 2011 ;
