Carbon Dioxide → 4-{[(Tert-butoxy)carbonyl]amino}pyridine-3-carboxylic acid

HRID 1059560Notes

Reaction equation

HRID 1059560 reaction equation
C([Li])CCC.[C:6]([O:10][C:11]([NH:13][C:14]1[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=1)=[O:12])([CH3:9])([CH3:8])[CH3:7].CCOCC.[C:25](=[O:27])=[O:26]>C1COCC1.C(O)(=O)C.O>[C:6]([O:10][C:11]([NH:13][C:14]1[C:15]([C:25]([OH:27])=[O:26])=[CH:16][N:17]=[CH:18][CH:19]=1)=[O:12])([CH3:9])([CH3:7])[CH3:8]

Participants

8

Reactant 4

HCID 280Carbon DioxideHCID 3283Diethyl EtherHCID 99902104-(Boc-amino)pyridineHCID 178418339Butyllithium

Product 1

HCID 221726234-{[(Tert-butoxy)carbonyl]amino}pyridine-3-carboxylic acidYield 54%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

n-Butyl lithium (2.18 M, 24 mL, 52.51 mmol) is added slowly to a solution of 4-(N-t-butoxycarbonylamino)-pyridine (4.08 g, 21 mmol) in THF (50 mL, stirred under N2 at −78° C. The solution is allowed to warm to 0° C., stirred for 3 h, then cooled again to −78° C. and poured into ether (100 mL) containing dry ice. The solution is warmed to room temperature with constant stirring. Water is added and the mixture is neutralized with acetic acid. The resulting solid is collected by vacuum filtration and dried in a vacuum oven to give 4-(N-t-butoxycarbonylamino)nicotinic acid (2.72 g, 54%) as a brown solid. 1H NMR (DMSO) δ 11.75 (1H, brs), 8.95 (1H, s), 8.50 (1H, d, J=6.0 Hz), 8.20 (1H, d, J=6.0 Hz), 1.49 (9H, s)

Workup

  1. temperatureto warm to 0° C.
  2. stirringstirred for 3 h
  3. temperaturecooled again to −78° C.
  4. temperatureThe solution is warmed to room temperature with constant stirring
  5. filtrationThe resulting solid is collected by vacuum filtration
  6. customdried in a vacuum oven

Sources & evidence

ORD record
ord-e2143a13a2d5422689369fd463eb5df8
Source dataset
uspto-grants-2003_02
Patent number
US06521620B1

Reaction notes

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