(1S,4R,6S)-6-(6-氯吡啶-3-基)-7-氮杂双环[2.2.1]庚烷合成路线 （共 15 条）
反应条件
tetraethylammonium metaperiodate in methanol; dichloromethane
参考文献
The United States of America as represented by the Secretary of the Department of Health and Human Services
Patent: US5314899 A1, 1994 ;
反应条件
1: n-BuLi / diethyl ether; tetrahydrofuran; hexane / 1.) -70 deg C, 20 min, 2.) -70 deg C, 2 h; -50 deg C, 30 min
2: KH / tetrahydrofuran / 1.) r.t., 20 min, 2.) r.t., 20 min
3: toluene / 2 h / Heating
4: H2 / PtO2 / ethyl acetate / 1 h / 2068.6 Torr
5: HCl / ethyl acetate / 1 h / 0 °C
View Scheme
参考文献
Fletcher, Stephen R.; Baker, Raymond; Chambers, Mark S.; Herbert, Richard H.; Hobbs, Sarah C.; et al.
Journal of Organic Chemistry, 1994 , vol. 59, # 7 p. 1771 - 1778
反应条件
1: 66 percent / Cs2CO3 / dimethylformamide / 40 h / 70 °C
2: 80percent m-CPBA / CH2Cl2 / 4 h / Ambient temperature
3: 78 percent / aq. K2CO3 / methanol / 72 h / Ambient temperature
4: 48 percent / 1-methyl-2-pyrrolidinone / 16 h / 180 °C
5: 5 N HCl, H2 / Pd(OH)2/C / ethanol / 6 h / 40 °C / 2068.6 Torr
6: 1 N NaOH / dioxane / 18 h / Ambient temperature
7: 43 percent / DMAP / CH2Cl2 / 18 h / Ambient temperature
8: 97 percent / KOH / ethanol / 2 h / Ambient temperature
9: 1.) oxalyl chloride, DMSO, 2.) Et3N / 1.) CH2Cl2, -70 deg C, 20 min
10: n-BuLi / diethyl ether; tetrahydrofuran; hexane / 1.) -70 deg C, 20 min, 2.) -70 deg C, 2 h; -50 deg C, 30 min
11: KH / tetrahydrofuran / 1.) r.t., 20 min, 2.) r.t., 20 min
12: toluene / 2 h / Heating
13: H2 / PtO2 / ethyl acetate / 1 h / 2068.6 Torr
14: HCl / ethyl acetate / 1 h / 0 °C
View Scheme
参考文献
Fletcher, Stephen R.; Baker, Raymond; Chambers, Mark S.; Herbert, Richard H.; Hobbs, Sarah C.; et al.
Journal of Organic Chemistry, 1994 , vol. 59, # 7 p. 1771 - 1778
反应条件
1: 80percent m-CPBA / CH2Cl2 / 4 h / Ambient temperature
2: 78 percent / aq. K2CO3 / methanol / 72 h / Ambient temperature
3: 48 percent / 1-methyl-2-pyrrolidinone / 16 h / 180 °C
4: 5 N HCl, H2 / Pd(OH)2/C / ethanol / 6 h / 40 °C / 2068.6 Torr
5: 1 N NaOH / dioxane / 18 h / Ambient temperature
6: 43 percent / DMAP / CH2Cl2 / 18 h / Ambient temperature
7: 97 percent / KOH / ethanol / 2 h / Ambient temperature
8: 1.) oxalyl chloride, DMSO, 2.) Et3N / 1.) CH2Cl2, -70 deg C, 20 min
9: n-BuLi / diethyl ether; tetrahydrofuran; hexane / 1.) -70 deg C, 20 min, 2.) -70 deg C, 2 h; -50 deg C, 30 min
10: KH / tetrahydrofuran / 1.) r.t., 20 min, 2.) r.t., 20 min
11: toluene / 2 h / Heating
12: H2 / PtO2 / ethyl acetate / 1 h / 2068.6 Torr
13: HCl / ethyl acetate / 1 h / 0 °C
View Scheme
参考文献
Fletcher, Stephen R.; Baker, Raymond; Chambers, Mark S.; Herbert, Richard H.; Hobbs, Sarah C.; et al.
Journal of Organic Chemistry, 1994 , vol. 59, # 7 p. 1771 - 1778
反应条件
1: 1.) oxalyl chloride, DMSO, 2.) Et3N / 1.) CH2Cl2, -70 deg C, 20 min
2: n-BuLi / diethyl ether; tetrahydrofuran; hexane / 1.) -70 deg C, 20 min, 2.) -70 deg C, 2 h; -50 deg C, 30 min
3: KH / tetrahydrofuran / 1.) r.t., 20 min, 2.) r.t., 20 min
4: toluene / 2 h / Heating
5: H2 / PtO2 / ethyl acetate / 1 h / 2068.6 Torr
6: HCl / ethyl acetate / 1 h / 0 °C
View Scheme
参考文献
Fletcher, Stephen R.; Baker, Raymond; Chambers, Mark S.; Herbert, Richard H.; Hobbs, Sarah C.; et al.
Journal of Organic Chemistry, 1994 , vol. 59, # 7 p. 1771 - 1778
反应条件
1: n-BuLi / diethyl ether; tetrahydrofuran; hexane / 1.) -70 deg C, 20 min, 2.) -70 deg C, 2 h; -50 deg C, 30 min
2: KH / tetrahydrofuran / 1.) r.t., 20 min, 2.) r.t., 20 min
3: toluene / 2 h / Heating
4: H2 / PtO2 / ethyl acetate / 1 h / 2068.6 Torr
5: HCl / ethyl acetate / 1 h / 0 °C
View Scheme
参考文献
Fletcher, Stephen R.; Baker, Raymond; Chambers, Mark S.; Herbert, Richard H.; Hobbs, Sarah C.; et al.
Journal of Organic Chemistry, 1994 , vol. 59, # 7 p. 1771 - 1778
反应条件
1.1: PPh3; HCOOH; Et3N / Pd(OAc)2 / tetrahydrofuran / 20 °C
1.2: L-selectride / tetrahydrofuran / -78 °C
1.3: NaOMe / 2-methyl-propan-2-ol
2.1: NaBH3CN; AcOH / methanol / -20 °C
3.1: Et3N; DMAP / CH2Cl2 / 0 °C
4.1: Zn; AcOH / tetrahydrofuran / 20 °C
5.1: CHCl3 / 60 °C
View Scheme
参考文献
Takemoto, Yoshiji; Miyabe, Hideto
Chimia, 2007 , vol. 61, # 5 p. 269 - 275
反应条件
1.1: (1R,2R)-1-[[3',5'-(CF3)2-C6H3]-NH-C(S)-NH]-2-NMe2-cC6H10 / toluene / 0 °C
2.1: KOH / ethanol / 0 °C
3.1: PPh3; HCOOH; Et3N / Pd(OAc)2 / tetrahydrofuran / 20 °C
3.2: L-selectride / tetrahydrofuran / -78 °C
3.3: NaOMe / 2-methyl-propan-2-ol
4.1: NaBH3CN; AcOH / methanol / -20 °C
5.1: Et3N; DMAP / CH2Cl2 / 0 °C
6.1: Zn; AcOH / tetrahydrofuran / 20 °C
7.1: CHCl3 / 60 °C
View Scheme
参考文献
Takemoto, Yoshiji; Miyabe, Hideto
Chimia, 2007 , vol. 61, # 5 p. 269 - 275
反应条件
1: 60 percent / LiAlH4 / tetrahydrofuran / 2 h / 0 °C
2: 88 percent / PCC / CH2Cl2 / 2 h / 23 °C
3: 89 percent / KHMDS, 18-crown-6*CH3CN / tetrahydrofuran / 1 h / -78 °C
4: 95 percent / toluene / 24 h / 190 °C
5: 100 percent / LiOH / tetrahydrofuran / 5 h / 23 °C
6: Et3N, (PhO)2P(=O)N3 / toluene / 2 h / 85 °C
7: 95 percent / 12 h / 85 °C
8: TBAF / tetrahydrofuran / 4 h / 55 °C
9: Et3N / CH2Cl2 / 0.5 h / 23 °C
10: 96 percent / Br2, Et4N(+)Br(-) / CH2Cl2 / 0.5 h / -78 °C
11: 75 percent / t-BuOK / tetrahydrofuran / 18 h / -78 - 4 °C
12: Bu3SnH, AIBN / benzene / 1.5 h / Heating
13: NaOMe / methanol / 2 h / 23 °C
View Scheme
参考文献
Corey, E. J.; Loh, Teck-Peng; AchyuthaRao, Sidduri; Daley, Donnette C.; Sarshar, Sepehr
Journal of Organic Chemistry, 1993 , vol. 58, # 21 p. 5600 - 5602
反应条件
1: 89 percent / KHMDS, 18-crown-6*CH3CN / tetrahydrofuran / 1 h / -78 °C
2: 95 percent / toluene / 24 h / 190 °C
3: 100 percent / LiOH / tetrahydrofuran / 5 h / 23 °C
4: Et3N, (PhO)2P(=O)N3 / toluene / 2 h / 85 °C
5: 95 percent / 12 h / 85 °C
6: TBAF / tetrahydrofuran / 4 h / 55 °C
7: Et3N / CH2Cl2 / 0.5 h / 23 °C
8: 96 percent / Br2, Et4N(+)Br(-) / CH2Cl2 / 0.5 h / -78 °C
9: 75 percent / t-BuOK / tetrahydrofuran / 18 h / -78 - 4 °C
10: Bu3SnH, AIBN / benzene / 1.5 h / Heating
11: NaOMe / methanol / 2 h / 23 °C
View Scheme
参考文献
Corey, E. J.; Loh, Teck-Peng; AchyuthaRao, Sidduri; Daley, Donnette C.; Sarshar, Sepehr
Journal of Organic Chemistry, 1993 , vol. 58, # 21 p. 5600 - 5602
