2-Fluoro-4-methylaniline → HCID 22025613, compound

HRID 1793003Notes

Reaction equation

HRID 1793003 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]([CH3:21])[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]([CH3:21])=[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 679842-Fluoro-4-methylanilineHCID 3029322,3,4-Trifluorobenzoic acidHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 22025613HCID 22025613, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2,3,4-Trifluorobenzoic acid and 2-fluoro-4-methylaniline were reacted in the presence of LiHMDS solution in THF by the general procedure of Example 1, Step B. After workup, 3,4-difluoro-2-[2-fluoro-4-methylanilino]benzoic acid was isolated as a crude pale brown solid which was reacted directly with 2-(aminooxy)ethanol and DMT-MM by the general procedure of Example 6, Step B below, then purified by column chromatography on silica gel (100% EtOAc as eluant) to give 3,4-difluoro-2-(2-fluoro-4-methylanilino)-N-(2-hydroxyethoxy)benzamide as a white solid (44%); m.p. (EtOAc/hexane) 134–139° C. 1H NMR [400 MHz, (CD3)2SO] [ ] 11.82 (v br s, 1H), 8.77 (br s, 1 H), 7.41 (ddd, J=8.1, 5.7, 1.6 Hz, 1 H), 7.13–7.00 (m, 2 H), 6.88 (dd, J=8.3, 1.1 Hz, 1 H), 6.82 (ddd, J=8.5, 8.5, 4.2 Hz, 1 H), 4.76 (v br s, 1 H), 3.86 (t, J=5.0 Hz, 2 H), 3.58 (J=5.0 Hz, 2 H), 2.25 (s, 3 H). Anal. calcd. for C16H15F3N2O3: C, 56.5; H, 4.4; N, 8.2. Found C, 56.3; H, 4.5; N, 8.2.

Sources & evidence

ORD record
ord-652bcc1582d54f0ca58d7b36a9a67c78
Source dataset
uspto-grants-2006_07
Patent number
US07078438B2

Reaction notes

Loading…