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

HRID 1793041Notes

Reaction equation

HRID 1793041 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)aniline2×

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-32e71b0cf85c4ae48b219b6ae0e5c41b
Source dataset
uspto-grants-2006_07
Patent number
US07078438B2

Reaction notes

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