2-(4-Ethynyl-2-fluoroanilino)-3,4-difluorobenzoic acid → 2-[(4-Ethyl-2-fluorophenyl)amino]-3,4-difluorobenzoic acid

HRID 2181428Notes

Reaction equation

HRID 2181428 reaction equation
[F:1][C:2]1[C:3]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]#[CH:20])=[CH:15][C:14]=2[F:21])=[C:4]([CH:8]=[CH:9][C:10]=1[F:11])[C:5]([OH:7])=[O:6]>C(O)C.[Pd]>[CH2:19]([C:16]1[CH:17]=[CH:18][C:13]([NH:12][C:3]2[C:2]([F:1])=[C:10]([F:11])[CH:9]=[CH:8][C:4]=2[C:5]([OH:7])=[O:6])=[C:14]([F:21])[CH:15]=1)[CH3:20]

Participants

4

Reactant 1

HCID 220256332-(4-Ethynyl-2-fluoroanilino)-3,4-difluorobenzoic acid

Product 1

HCID 220256532-[(4-Ethyl-2-fluorophenyl)amino]-3,4-difluorobenzoic acidYield 92.1%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

The product of Step C, 3,4-difluoro-2-[(4-ethynyl-2-fluorophenyl)amino]benzoic acid (300 mg, 1.03 mmol), was dissolved in absolute ethanol (30 mL) and 5% Pd/C (30 mg) added. This mixture was stirred under an atmosphere of hydrogen (60 psi) for 2 hours at room temperature. The Pd/C was removed over Celite®, which was washed well with additional ethanol, then the solvent removed from the resultant filtrate under reduced pressure to afford 2-[(4-ethyl-2-fluorophenyl)amino]-3,4-difluorobenzoic acid as an off-white solid (280 mg, 92%); m.p. (EtOAc/hexanes) 199-201° C. 1H NMR [400 MHz, (CD3)2SO] δ 14.10 (br s, 1 H), 9.31 (br s, 1 H), 7.80 (ddd, J=8.5, 6.1, 1.9 Hz, 1 H), 7.09 (dd, J=12.4, 1.5 Hz, 1 H), 7.04-6.92 (m, 3 H), 2.52 (q, J=7.6 Hz, 2 H), 1.17 (t, J=7.5 Hz, 3 H).

Workup

  1. customThe Pd/C was removed over Celite®, which
  2. washwas washed well with additional ethanol
  3. customthe solvent removed from the resultant filtrate under reduced pressure

Sources & evidence

ORD record
ord-7d3f837182fe49919fd20cb756ce2372
Source dataset
uspto-grants-2005_05
Patent number
US06891066B2

Reaction notes

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