6,7-二甲氧基-1(S)-[2-[4-(三氟甲基)苯基]乙基]-1,2,3,4-四氢异喹啉合成路线 （共 14 条）
反应条件
potassium carbonate; sodium hydroxide in methylisobutylketone (MIBK) T=70 - 90°C;
参考文献
De Vries, Maria Andreas Hendrikus; Domin, Doris; Helms, Matthias; Imboden, Chistoph; Koberstein, Ralph; Nazir, Zarghun; Skranc, Wolfgang; Stanek, Michael; Tschebull, Wilhelm; Verzijl, Maria Gerardus Karel; Stichler, Juergen
Patent: US2010/10226 A1, 2010 ;
Location in patent: Page/Page column 13 ;
反应条件
N-ethyl-N,N-diisopropylamine in tetrahydrofuran T=60°C; 168 h; Product distribution / selectivity;
参考文献
ACTELION PHARMACEUTICALS LTD
Patent: WO2005/118548 A1, 2005 ;
Location in patent: Page/Page column 29 ;
WO 2005/118548 A1
反应条件
sodium hydroxide in methylisobutylketone (MIBK); water
T=20°C;
参考文献
ACTELION PHARMACEUTICALS LTD
Patent: WO2009/83899 A2, 2009 ;
Location in patent: Page/Page column 28 ;
Title/Abstract Full Text Show Details
ACTELION PHARMACEUTICALS LTD
Patent: WO2009/83903 A1, 2009 ;
Location in patent: Page/Page column 28 ;
反应条件
hydrogen; N-ethyl-N,N-diisopropylamine; di-μ-chloro-bis(η4-1,5-cyclooctadiene)diiridium; C24H22NO2P in ethyl acetate
T=50°C; P=18751.9 Torr;
参考文献
ACTELION PHARMACEUTICALS LTD
Patent: WO2009/83899 A2, 2009 ;
Location in patent: Page/Page column 27 ;
Title/Abstract Full Text Show Details
ACTELION PHARMACEUTICALS LTD
Patent: WO2009/83903 A1, 2009 ;
Location in patent: Page/Page column 27 ;
反应条件
1: 6,7-Dimethoxy-1-methyl-3,4-dihydroisoquinoline With n-butyllithium; diisopropylamine in tetrahydrofuran; hexane
T=0 - 20°C; 1 h;
2: 4-(trifluoromethyl)-benzyl bromide in tetrahydrofuran; hexane
T=0°C; 1 h;
3: With (R,R)-MESsDPEN; formic acid; triethylamine; [Ru2(p-PriC6H4Me)2(μ-Cl)Cl]2 in acetonitrile
48 h; Product distribution / selectivity;
参考文献
ACTELION PHARMACEUTICALS LTD
Patent: WO2005/118548 A1, 2005 ;
Location in patent: Page/Page column 23-24 ;
WO 2005/118548 A1
反应条件
formic acid; [RuCl(η6-p-cymene)(N-tosyl-1,2-diphenylethylenediamine)]; triethylamine in dichloromethane
T=28 - 32°C; P=412.541 Torr; 20 h; Large scale; SolventTemperatureTime; enantioselective reaction;
参考文献
Verzijl, Gerard K. M.; De Vries, Andre H. M.; De Vries, Johannes G.; Kapitan, Peter; Dax, Thomas; Helms, Matthias; Nazir, Zarghun; Skranc, Wolfgang; Imboden, Christoph; Stichler, Juergen; Ward, Richard A.; Abele, Stefan; Lefort, Laurent
Organic Process Research and Development, 2013 , vol. 17, # 12 p. 1531 - 1539
反应条件
sodium hydrogencarbonate in dichloromethane; water
参考文献
ACTELION PHARMACEUTICALS LTD
Patent: WO2004/85403 A1, 2004 ;
Location in patent: Page 37-38 ;
WO 2004/085403 A1
反应条件
formic acid; [RuCl(η6-p-cymene)(N-tosyl-1,2-diphenylethylenediamine)]; triethylamine in ethyl acetate
T=23°C; 40 h; Large scale; SolventTemperatureTime; enantioselective reaction;
参考文献
Verzijl, Gerard K. M.; De Vries, Andre H. M.; De Vries, Johannes G.; Kapitan, Peter; Dax, Thomas; Helms, Matthias; Nazir, Zarghun; Skranc, Wolfgang; Imboden, Christoph; Stichler, Juergen; Ward, Richard A.; Abele, Stefan; Lefort, Laurent
Organic Process Research and Development, 2013 , vol. 17, # 12 p. 1531 - 1539
反应条件
1.1: sodium hydride / N,N-dimethyl-formamide / 6 h / 0 - 20 °C
2.1: sodium hydride; hydrogenchloride / methanol; water; 1,4-dioxane / 0.5 h / 0 - 20 °C
3.1: triethylamine / dichloromethane / 0.17 h
3.2: 1 h / 20 °C
4.1: osmium(VIII) oxide; 2,6-dimethylpyridine; sodium periodate / 1,4-dioxane / 2 h
5.1: magnesium; iodine / tetrahydrofuran / 0.5 h / 20 °C / |Inert atmosphere
5.2: 2 h / 0 °C / |Inert atmosphere
6.1: triethylamine / dichloromethane / 1 h / 0 °C / |Inert atmosphere
7.1: lithium aluminium tetrahydride / tetrahydrofuran / 1 h / 0 °C
8.1: trimethylsilyl trifluoromethanesulfonate; sodium hydrogencarbonate / dichloromethane / 1 h / 20 °C
View Scheme
参考文献
Reddy, N. Siva Senkar; Reddy, B.V. Subba
Tetrahedron Letters, 2014 , vol. 55, # 20 p. 3143 - 3145
反应条件
1.1: sodium hydride; hydrogenchloride / methanol; water; 1,4-dioxane / 0.5 h / 0 - 20 °C
2.1: triethylamine / dichloromethane / 0.17 h
2.2: 1 h / 20 °C
3.1: osmium(VIII) oxide; 2,6-dimethylpyridine; sodium periodate / 1,4-dioxane / 2 h
4.1: magnesium; iodine / tetrahydrofuran / 0.5 h / 20 °C / |Inert atmosphere
4.2: 2 h / 0 °C / |Inert atmosphere
5.1: triethylamine / dichloromethane / 1 h / 0 °C / |Inert atmosphere
6.1: lithium aluminium tetrahydride / tetrahydrofuran / 1 h / 0 °C
7.1: trimethylsilyl trifluoromethanesulfonate; sodium hydrogencarbonate / dichloromethane / 1 h / 20 °C
View Scheme
参考文献
Reddy, N. Siva Senkar; Reddy, B.V. Subba
Tetrahedron Letters, 2014 , vol. 55, # 20 p. 3143 - 3145
