反应详情

温度

-78 °C

A solution of 1-tert-butyl 4-ethyl 5-hydroxy-2,3,6,7-tetrahydro-1H-azepine-1,4-dicarboxylate (14.11 mmol, 4.02 g) in anhydrous THF (15 ml) was added to a stirred solution of freshly prepared iPr2NLi (43.74 mmol) in anhydrous THF (95 ml) at −78° C. The reaction mixture was stirred at −78° C. for 1 h and HMPA (42.33 mmol, 7.38 ml) was added followed by MeI (14.11 mmol, 0.97 ml). The reaction mixture was slowly warmed to room temperature and stirred overnight before being quenched with sat. aq. NH4Cl. After addition of water, the reaction mixture was extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The crude mixture was treated with NH4OAc and MeOH in the same manner described above and furnished 1-tert-butyl 4-ethyl 5-amino-6-methyl-2,3,6,7-tetrahydro-1H-azepine-1,4-dicarboxylate in 76% yield. MS (ESI) m/z 299 [M+1]+7-tert-Butyl 3-ethyl 4-hydroxy-9-methyl-2-oxo-1,2,5,6,8,9-hexahydro-7H-pyrido[2,3-d]azepine-3,7-dicarboxylate was obtained in comparable yields from 1-tert-butyl 4-ethyl 5-amino-6-methyl-2,3,6,7-tetrahydro-1H-azepine-1,4-dicarboxylate applying the cyclization procedure described for the synthesis of tert-butyl 4-hydroxy-2-oxo-1,2,5,6,8,9-hexahydro-7H-pyrido[2,3-d]azepine-7-carboxylate. 1H-NMR (CDCl3) δ 13.97 (1H), 11.54 (1H), 4.47 (2H), 3.94 (1H), 3.82 (1H), 3.41 (1H), 3.15 (3H), 2.61 (1 H), 1.46 (9 H), 1.42 (3H), 1.31 (3H) ppm. tert-Butyl 4-hydroxy-9-methyl-2-oxo-1,2,5,6,8,9-hexahydro-7H-pyrido[2,3-d]azepine-7-carboxylate was obtained in comparable yields from 7-tert-butyl 3-ethyl 4-hydroxy-9-methyl-2-oxo-1,2,5,6,8,9-hexahydro-7H-pyrido[2,3-d]azepine-3,7-dicarboxylate applying the decarboxylation procedure described for the synthesis of tert-butyl 4-hydroxy-2-oxo-1,2,5,6,8,9-hexahydro-7H-pyrido[2,3-d]azepine-7-carboxylate. 1H-NMR (DMSO-d6) δ 10.75 (2H), 5.50 (1H), 3.61 (2H), 3.51 (1H), 3.06 (2H), 2.91 (1H), 2.48 (1H), 1.39 (9 H), 1.12 (3 H) ppm.

1. temperatureThe reaction mixture was slowly warmed to room temperature
2. stirringstirred overnight
3. custombefore being quenched with sat. aq. NH4Cl
4. additionAfter addition of water
5. extractionthe reaction mixture was extracted with EtOAc
6. washThe organic layer was washed with brine
7. dry with materialdried over Na2SO4
8. concentrationconcentrated under reduced pressure
9. additionThe crude mixture was treated with NH4OAc and MeOH in the same manner