Triethylamine → 2-(2,4-Difluoroanilino)-4,5-difluorobenzoic acid

HRID 2165349Notes

Reaction equation

C(N(CC)CC)C.[F:8][C:9]1[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:10]=1[NH2:11].Cl[C:18]1[CH:26]=[C:25]([F:27])[C:24]([F:28])=[CH:23][C:19]=1[C:20]([OH:22])=[O:21]>CN(C=O)C.[Cu]>[F:8][C:9]1[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:10]=1[NH:11][C:18]1[CH:26]=[C:25]([F:27])[C:24]([F:28])=[CH:23][C:19]=1[C:20]([OH:22])=[O:21]

Participants

Conditions

Temperature: 85 °C

Procedure

A suspension of triethyl amine (15 ml, 0.11 mol), 2,4-difluoroaniline (25 ml, 0.24 mol), copper bronze (2.7 g., 0.04 mol), in hot DMF (25 ml) was treated with a solution of 2-chloro-4,5-difluorobenzoic acid (23 g., 0.12 mol) in 25 ml of DMF and the temperature was maintained at 85° C. for 8 hours. The reaction mixture was allowed to cool to room temperature and was then stirred overnight. The reaction mixture was evaporated in vacuo and the residue was partitioned between ether and aqueous ammonium chloride. The organic phase was washed with 2N HCl and saturated aqueous lithium chloride solution. The ether was dried over sodium sulfate, treated with darco and then filtered and evaporated. The residue was crystallized from hexane-ether to afford 21.6 g (62%) of 2-(2,4-difluorophenylamino)-4,5-difluorobenzoic acid; m.p.: 215°-216° C.

Workup

temperatureto cool to room temperature
customThe reaction mixture was evaporated in vacuo
customthe residue was partitioned between ether and aqueous ammonium chloride
washThe organic phase was washed with 2N HCl and saturated aqueous lithium chloride solution
dry with materialThe ether was dried over sodium sulfate
additiontreated with darco
filtrationfiltered
customevaporated
customThe residue was crystallized from hexane-ether

Sources & evidence

ORD record: ord-b76600926ac7498787defbae04ff9c87
Source dataset: uspto-grants-1990_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04939290

Reaction notes

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