反应详情

温度

-78 °C

n-Buli (1.6 M soln, 155 mL, 249 mmol) was added to a stirred solution of TMEDA (37.36 mL, 249 mmol) in THF at −40° C. The solution was allowed to come at room temperature over 10 min and stirred for another 10 min. The solution was cooled to −78° C. A solution of pyridine-4-yl-carbamic acid-tert-butyl ester (117) (22 g, 113.26 mmol) in THF was added slowly. The solution was allowed to come at room temperature within 3 h. After stirring at room temperature for 15 min the solution was again cooled to −78° C. and a freshly crushed dry ice was added. The solution was allowed to come at room temperature, stirred for 30 min and poured into ice cold 10% NH4Cl solution. The solution was basified by 1N NaOH solution and washed by dichloromethane. The pH of aqueous phase was adjusted to 4 by cold 10% HCl solution. The solids formed were filtered, washed by water and dried under vacuum at room temperature to yield 16.3 g (30%) 4-tert-butoxycarbonylamino-nicotinic acid (118) as white solids. MP: 260° C.; 1H-NMR (DMSO-d6): δ 1.49 (s, 9H), 8.23 (d, J=6.0 Hz, 1H), 8.55 (d, J=6.0 Hz, 1H), 8.96 (s, 1H); EIMS m/z 238 (M+1).

1. waitto come at room temperature within 3 h
2. stirringAfter stirring at room temperature for 15 min the solution
3. temperaturewas again cooled to −78° C.
4. customto come at room temperature
5. stirringstirred for 30 min
6. washwashed by dichloromethane
7. customThe solids formed
8. filtrationwere filtered
9. washwashed by water
10. customdried under vacuum at room temperature