2,3,4-Trifluorobenzoic acid → 3,4-Difluoro-2-[[2-fluoro-4-(methylthio)phenyl]amino]benzoic acid

HRID 2181470Notes

Reaction equation

HRID 2181470 reaction equation
F[C:2]1[C:10]([F:11])=[C:9]([F:12])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[F:13][C:14]1[CH:20]=[C:19]([S:21][CH3:22])[CH:18]=[CH:17][C:15]=1[NH2:16].[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[F:11][C:10]1[C:2]([NH:16][C:15]2[CH:17]=[CH:18][C:19]([S:21][CH3:22])=[CH:20][C:14]=2[F:13])=[C:3]([CH:7]=[CH:8][C:9]=1[F:12])[C:4]([OH:6])=[O:5]

Participants

5

Reactant 3

HCID 3029322,3,4-Trifluorobenzoic acidHCID 2733832Lithium HexamethyldisilazideHCID 220256172-Fluoro-4-(methylsulfanyl)aniline

Product 1

HCID 220256943,4-Difluoro-2-[[2-fluoro-4-(methylthio)phenyl]amino]benzoic acidYield 52%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2,3,4-Trifluorobenzoic acid and the product of Example 26, Step B, 2-fluoro-4-methylthioaniline, were reacted in the presence of LiHMDS solution in THF by the general procedure of Example 1, Step B. After workup, this material was purified by dry flash column chromatography on silica (0.5% Et2O in 1:1 CH2Cl2/hexanes as eluant) to afford 3,4-difluoro-2-[[2-fluoro-4-(methylthio)phenyl]amino]benzoic acid as a cream solid (52%); m.p. (Et2O/hexanes) 210-220° C. 1H NMR (400 MHz, CDCl3) δ 13.70 (br s, 1 H), 9.24 (br s, 1 H), 7.81 (ddd, J=9.0, 6.1, 2.1 Hz, 1 H), 7.20 (dd, J=11.8, 1.9 Hz, 1 H), 7.03-6.99 (m, 3 H), 2.47 (s, 3 H). Anal. Calcd for C14H10F3NO2S-0.125 Et2O: C, 54.0; H, 3.5; N, 4.3. Found: C, 54.2; H, 3.3; N, 4.5.

Workup

  1. customAfter workup, this material was purified
  2. customby dry flash column chromatography on silica (0.5% Et2O in 1:1 CH2Cl2/hexanes as eluant)

Sources & evidence

ORD record
ord-1f40a34939f44ecda7c50426c7674ee9
Source dataset
uspto-grants-2005_05
Patent number
US06891066B2

Reaction notes

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