4',5'-二氢-螺[哌啶-4,7'-[7H]噻吩并[2,3-c]吡喃]-1-羧酸叔丁酯合成路线 （共 2 条）
反应条件
1.1: 2,2,6,6-tetramethyl-piperidine; n-butyllithium / hexane; tetrahydrofuran / -78 - -70 °C / Inert atmosphere 1.2: -20 °C / Inert atmosphere 2.1: hydrogenchloride; water / isopropyl alcohol / 6.5 h / 45 °C View Scheme
参考文献
ELI LILLY AND COMPANY; BENITO COLLADO, Ana Belen; DIAZ BUEZO, Nuria; JIMENEZ-AGUADO, Alma Maria; LAFUENTE BLANCO, Celia; MARTINEZ-GRAU, Maria Angeles; PEDREGAL-TERCERO, Concepcion; TOLEDO ESCRIBANO, Miguel Angel
Patent: WO2011/60217 A1, 2011 ;
WO 2011/060217 A1
反应条件
1.1: n-butyllithium / tetrahydrofuran; hexane / 1 h / -78 °C / Inert atmosphere
1.2: -78 - 20 °C / Inert atmosphere
2.1: hydrogenchloride / 1,4-dioxane; dichloromethane / 3 h / 20 °C
3.1: triethylamine / tetrahydrofuran / 20 h / 65 °C
4.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -78 °C
4.2: 0.5 h / -78 °C
4.3: 2 h / -78 - 0 °C
5.1: trifluoroacetic acid / dichloromethane / 16 h / 20 °C
6.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine / dichloromethane / 20 °C
7.1: N,N-diethylaniline / ethanol; hexane / Resolution of racemate
View Scheme
参考文献
Pike, Victor W.; Rash, Karen S.; Chen, Zhaogen; Pedregal, Concepcion; Statnick, Michael A.; Kimura, Yasuyuki; Hong, Jinsoo; Zoghbi, Sami S.; Fujita, Masahiro; Toledo, Miguel A.; Diaz, Nuria; Gackenheimer, Susan L.; Tauscher, Johannes T.; Barth, Vanessa N.; Innis, Robert B.
Journal of Medicinal Chemistry, 2011 , vol. 54, # 8 p. 2687 - 2700
