Potassium Carbonate → 2-(4-Ethynyl-2-fluoroanilino)-3,4-difluorobenzoic acid

HRID 1792997Notes

Reaction equation

HRID 1792997 reaction equation
[F:1][C:2]1[C:3]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]#[C:20][Si](C)(C)C)=[CH:15][C:14]=2[F:25])=[C:4]([CH:8]=[CH:9][C:10]=1[F:11])[C:5]([OH:7])=[O:6].C([O-])([O-])=O.[K+].[K+]>CO>[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:25])=[C:4]([CH:8]=[CH:9][C:10]=1[F:11])[C:5]([OH:7])=[O:6]

Participants

4

Reactant 2

HCID 11430Potassium CarbonateHCID 220256313,4-Difluoro-2-[[2-fluoro-4-(trimethylsilylethynyl)phenyl]amino]benzoic acid

Product 1

HCID 220256332-(4-Ethynyl-2-fluoroanilino)-3,4-difluorobenzoic acidYield 99%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The product of Step B, 3,4-difluoro-2-[[2-fluoro-4-(trimethylsilylethynyl)phenyl]amino]benzoic acid (3.99 g, 11.0 mmol), was dissolved in MeOH (200 mL), to which was added K2CO3 (3.03 g, 22.0 mmol). This mixture was stirred at room temperature for 15 hours, then the reaction solvent removed under reduced pressure. The resulting residue was dissolved in water (50 mL), to which was added 1 M HCl until the pH=4. The resulting pale brown precipitate was collected by filtration and dried to afford the desired product (3.17 g, 99%); m.p. (EtOAc/hexanes) 160–162° C. 1H NMR [400 MHz, (CD3)2SO] δ 13.70 (br s, 1 H), 9.24 (br s, 1 H), 7.82 (ddd, J=9.2, 6.1, 2.1 Hz, 1 H), 7.38 (dd, J=12.0, 1.9, 1 H), 7.21 (ddd, J=8.4, 1.9, 0.8 Hz, 1 H), 7.16 (td, J=9.5, 7.3 Hz, 1 H), 6.96 (ddd, J=8.9, 8.4, 5.4 Hz, 1 H), 4.15 (s, 1 H). Anal. Calcd for C15H8F3NO2: C, 62.4; H, 3.1; N, 4.7. Found: C, 62.4; H, 3.2; N, 4.6.

Workup

  1. customthe reaction solvent removed under reduced pressure
  2. dissolutionThe resulting residue was dissolved in water (50 mL), to which
  3. additionwas added 1 M HCl until the pH=4
  4. filtrationThe resulting pale brown precipitate was collected by filtration
  5. customdried

Sources & evidence

ORD record
ord-fc919ded7e0b4f518a6fe0d13ab6a378
Source dataset
uspto-grants-2006_07
Patent number
US07078438B2

Reaction notes

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