Acetic Acid → 2-(4-Fluoroanilino)pyridine-4-carboxylic acid

HRID 2374019Notes

Reaction equation

HRID 2374019 reaction equation
F[C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][N:10]=1)[C:5]([OH:7])=[O:6].[F:11][C:12]1[CH:18]=[CH:17][C:15]([NH2:16])=[CH:14][CH:13]=1.[H-].[Na+].C(O)(=O)C>CN(C=O)C>[F:11][C:12]1[CH:18]=[CH:17][C:15]([NH:16][C:2]2[CH:3]=[C:4]([CH:8]=[CH:9][N:10]=2)[C:5]([OH:7])=[O:6])=[CH:14][CH:13]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 97314-FluoroanilineHCID 24758Sodium hydrideHCID 3453602-Fluoroisonicotinic acid

Product 1

HCID 284007812-(4-Fluoroanilino)pyridine-4-carboxylic acidYield 86.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

To a mixture of 2-fluoro-isonicotinic acid (Aldrich, 423 mg, 3.0 mmol) and 4-fluoroaniline (555 mg, 5.0 mmol) in DMF (18 mL) at rt was added NaH (500 mg of 60% in oil), and the mixture was heated at 85° C. for 75 min. Acetic acid (0.7 mL) was added to the reaction mixture and it was concentrated in vacuo. To the residue were added EtOAc (100 mL) and water (20 mL), stirred for 20 min and the solid was filtered, washed with EtOAc and dried to obtain the desired product (600 mg, 50%) as a tan solid. 1H NMR (DMSO-d6) δ 8.98 (s, 1H), 8.43 (s, 1H), 8.04 (d, 1H, J=4.9 Hz), 7.69 (dd, 2H, J=8.8, 4.9 Hz), 7.24 (s, 1H), 7.05 (dd, 2H, J=8.2, 6.0 Hz); MS(ESI+) m/z 233.3 (M+H)+.

Workup

  1. concentrationwas concentrated in vacuo
  2. additionTo the residue were added EtOAc (100 mL) and water (20 mL)
  3. filtrationthe solid was filtered
  4. washwashed with EtOAc
  5. customdried

Sources & evidence

ORD record
ord-95e53c97c671479daf0d019bfe6e02ce
Source dataset
uspto-grants-2008_12
Patent number
US07459562B2

Reaction notes

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