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

HRID 2237240Notes

Reaction equation

HRID 2237240 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-a1dd433f499b49b9b8d2fd21affe114b
Source dataset
uspto-grants-2010_05
Patent number
US07714138B2

Reaction notes

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