Reaction equation
CN(CCN(C)C)C.[C:9]([O:13][C:14](=[O:22])[NH:15][C:16]1[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=1)([CH3:12])([CH3:11])[CH3:10].[C:23](=[O:25])=[O:24].[OH-].[Na+]>C1COCC1>[C:9]([O:13][C:14]([NH:15][C:16]1[C:21]([C:23]([OH:25])=[O:24])=[CH:20][N:19]=[CH:18][CH:17]=1)=[O:22])([CH3:12])([CH3:10])[CH3:11]Participants
Conditions
- Temperature
- -78 °C
Procedure
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).
Workup
- waitto come at room temperature within 3 h
- stirringAfter stirring at room temperature for 15 min the solution
- temperaturewas again cooled to −78° C.
- customto come at room temperature
- stirringstirred for 30 min
- washwashed by dichloromethane
- customThe solids formed
- filtrationwere filtered
- washwashed by water
- customdried under vacuum at room temperature
Sources & evidence
- ORD record
- ord-5aa9006f4d4f4fdf9c83d169eef854be
- Source dataset
- uspto-grants-2008_04
- Patent number
- US07361760B2
Linked notes
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