N-Boc-4-哌啶甲酸乙酯合成路线 （共 67 条）
反应条件
1.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.5 h / -78 °C / |Inert atmosphere 1.2: 4 h / -78 - -60 °C / |Inert atmosphere 2.1: hydrogen; ammonia / ethanol / 48 h / 20 °C / 5171.62 Torr / |Autoclave 3.1: hydrogenchloride / dichloromethane; 1,4-dioxane / 18 h / 20 °C / |Inert atmosphere View Scheme
参考文献
Betschart, Claudia; Hintermann, Samuel; Behnke, Dirk; Cotesta, Simona; Fendt, Markus; Gee, Christine E.; Jacobson, Laura H.; Laue, Grit; Ofner, Silvio; Chaudhari, Vinod; Badiger, Sangamesh; Pandit, Chetan; Wagner, Juergen; Hoyer, Daniel
Journal of Medicinal Chemistry, 2013 , vol. 56, # 19 p. 7590 - 7607
反应条件
1.1: lithium diisopropyl amide / hexane; tetrahydrofuran / 0.5 h / -78 °C 1.2: 4 h / -78 - -60 °C 1.3: -60 °C 2.1: hydrogen; ammonia / Raney Ni / ethanol / 48 h / 20 °C / 5171.62 Torr / autoclave View Scheme
参考文献
Betschart, Claudia; Hintermann, Samuel; Behnke, Dirk; Cotesta, Simona; Fendt, Markus; Gee, Christine E.; Jacobson, Laura H.; Laue, Grit; Ofner, Silvio; Chaudhari, Vinod; Badiger, Sangamesh; Pandit, Chetan; Wagner, Juergen; Hoyer, Daniel
Journal of Medicinal Chemistry, 2013 , vol. 56, # 19 p. 7590 - 7607
反应条件
1.1: KHMDS / tetrahydrofuran / -78 °C
1.2: tetrahydrofuran / 1 h / -78 °C
2.1: O3 / methanol; CH2Cl2 / -78 °C
2.2: NaBH4 / 3 h / -78 - 20 °C
3.1: p-TsOH / toluene / 3 h / Heating
4.1: DIBAL-H / CH2Cl2 / 5 h / -78 - 0 °C
5.1: PPh3; diethyl azodicarboxylate / tetrahydrofuran / 16 h / 0 - 20 °C
View Scheme
参考文献
Cooper, Laura C.; Carlson, Emma J.; Castro, Jose L.; Chicchi, Gary G.; Dinnell, Kevin; Di Salvo, Jerry; Elliott, Jason M.; Hollingworth, Gregory J.; Kurtz, Marc M.; Ridgill, Mark P.; Rycroft, Wayne; Tsao, Kwei-Lan; Swain, Christopher J.
Bioorganic and Medicinal Chemistry Letters, 2002 , vol. 12, # 13 p. 1759 - 1762
反应条件
1.1: LDA / tetrahydrofuran / 1 h / -60 - -40 °C
1.2: 99 percent / tetrahydrofuran / 1 h / -40 - 20 °C
2.1: 99 percent / H2 / Ra-Ni / ethanol / 20 h / 50 °C / 37503 Torr
3.1: 83 percent / toluene / 18 h / Heating
4.1: 68 percent / TFA / CH2Cl2 / 0.25 h / 0 °C
View Scheme
参考文献
Krafft, Eva A.; Kurt, Anke; Maier, Axel; Thomas, Andrew W.; Zimmerli, Daniel
Synthesis, 2005 , # 19 art. no. C05905SS, p. 3245 - 3252
反应条件
1.1: N-ethyl-N,N-diisopropylamine; n-butyllithium / tetrahydrofuran / 1.25 h / -75 - -35 °C / Inert atmosphere
1.2: -75 - 20 °C / Inert atmosphere
2.1: trifluoroacetic acid / dichloromethane / 6 h / 20 °C
View Scheme
参考文献
HETERO RESEARCH FOUNDATION
Patent: US2011/15196 A1, 2011 ;
反应条件
1: ethyl 1-tert-butyloxycarbonyl-4-piperidinecarboxylate With lithium diisopropyl amide in tetrahydrofuran
T=-78 - -40°C; 1 h;
2: 4-bromomethyl-fluorobenzene in tetrahydrofuran
T=-78°C; 2 h; Product distribution / selectivity;
参考文献
KHAMRAI, Uttam; Ronsheim, Matthew; Karak, Sumit Kumar
Patent: US2010/152160 A1, 2010 ;
Location in patent: Page/Page column 77 ;
US 20100152160 A1
反应条件
1: ethyl 1-tert-butyloxycarbonyl-4-piperidinecarboxylate With lithium diisopropyl amide in tetrahydrofuran; n-heptane; ethylbenzene
T=-5°C; Inert atmosphere;
2: alpha-bromoacetonitrile in tetrahydrofuran; n-heptane; ethylbenzene
T=-5 - 20°C;
参考文献
F. HOFFMANN-LA ROCHE AG; ACKERMANN, Jean; CONTE, Aurelia; HUNZIKER, Daniel; NEIDHART, Werner; NETTEKOVEN, Matthias; SCHULZ-GASCH, Tanja; WERTHEIMER, Stanley
Patent: WO2010/130665 A1, 2010 ;
Location in patent: Page/Page column 136-137 ;
WO 2010/130665 A1
