Methyl 4-aminobenzoate → HCID 12135107, compound

HRID 2181455Notes

Reaction equation

HRID 2181455 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].[NH2:13][C:14]1[CH:23]=[CH:22][C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:16][CH:15]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[F:11][C:10]1[C:2]([NH:13][C:14]2[CH:15]=[CH:16][C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:22][CH:23]=2)=[C:3]([CH:7]=[CH:8][C:9]=1[F:12])[C:4]([OH:6])=[O:5]

Participants

5

Reactant 3

HCID 12082Methyl 4-aminobenzoateHCID 3029322,3,4-Trifluorobenzoic acidHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 12135107HCID 12135107, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2,3,4-Trifluorobenzoic acid and methyl 4-aminobenzoate were reacted in the presence of LiHMDS solution in THF by the general procedure of Example 1, Step B, to afford after workup, crude 3,4-difluoro-2-[[4-(methoxycarbonyl)-phenyl]amino]benzoic acid as a cream solid. This material was then coupled directly with 2-(aminooxy)ethanol by the general procedure of Example 1, Step E, and purified on flash silica (10% EtOAc as eluant) to give methyl 4-[[2,3-difluoro-6-[[(2-hydoxyethoxy)amino]carbonyl]phenyl]amino]benzoate (48%) as a white solid; m.p. (EtOAc/hexanes) 158-160° C. 1H NMR [400 MHz, (CD3)2SO] δ 11.64 (br s, 1 H), 8.76 (br s, 1 H), 7.78 (d, J=8.8 Hz, 2 H), 7.41-7.27 (m, 2 H), 6.80 (dd, J=8.8, 1.8 Hz, 2 H), 4.67 (br s, 1 H), 3.78 (s, 3 H), 3.76 (t, J=4.8 Hz, 2 H), 3.50 (t, J=4.6 Hz, 2 H). Anal. Calcd for C17H16F2N2O5: C, 55.7; H, 4.4; N, 7.7. Found: C, 55.7; H, 4.4; N, 7.6. Step B: Preparation of 4-[[2,3-difluoro-6-[[(2-hydroxyethoxy)amino]carbonyl]-phenyl]amino]benzoic acid

Sources & evidence

ORD record
ord-aded7bb04b574b568146a9d197db34ed
Source dataset
uspto-grants-2005_05
Patent number
US06891066B2

Reaction notes

Loading…