2,3,4-Trifluorobenzoic acid → HCID 12135109, compound

HRID 2181465Notes

Reaction equation

HRID 2181465 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]([C:21]#[C:22][CH2:23][O:24][CH3:25])[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]([C:21]#[C:22][CH2:23][O:24][CH3:25])=[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 22025687HCID 22025687, compound

Product 1

HCID 12135109HCID 12135109, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2,3,4-Trifluorobenzoic acid and the product of Example 25, Step A, 2-fluoro-4-(3-methoxy-1-propynyl)aniline, were reacted in the presence of LiHMDS solution in THF by the general procedure of Example 1, Step B. After workup, followed by purification by chromatography on silica gel (10% EtOAc/hexanes as eluant), 3,4-difluoro-2-[[2-fluoro-4-(3-methoxy-1-propynyl)phenyl]amino]-benzoic acid was isolated (62%) as a pale yellow solid; m.p. (EtOAc/hexanes) 221-223° C. 1H NMR [400 MHz, (CD3)2SO] δ 13.60 (br s, 1 H), 9.27 (br s, 1 H), 7.85-7.79 (m, 1H,), 7.36 (dd, J=12.0, 1.8 Hz, 1 H), 7.20 (dd, J=8.3, 1.5 Hz, 1 H), 7.18-7.11 (m, 1 H), 6.96 (td, 8.8, 5.5 Hz, 1 H), 4.31 (s, 2 H), 3.32 (s, 3H ). Anal. Calcd for C17H12F3NO3: C, 60.9; H, 3.6; N, 4.2. Found: C, 61.4; H, 3.6; N, 4.2. Step C: Preparation of 3,4-difluoro-2-[[2-fluoro-4-(3-methoxypropyl)phenyl]-amino]benzoic acid

Workup

  1. customAfter workup, followed by purification by chromatography on silica gel (10% EtOAc/hexanes as eluant)

Sources & evidence

ORD record
ord-fd535465446845438f29357f2fbeab10
Source dataset
uspto-grants-2005_05
Patent number
US06891066B2

Reaction notes

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