2-Fluoro-4-iodoaniline → 3,4-Difluoro-2-(2-fluoro-4-iodophenylamino)-5-nitrobenzoic acid

HRID 1161783Notes

Reaction equation

[F:1][C:2]1[CH:8]=[C:7]([I:9])[CH:6]=[CH:5][C:3]=1[NH2:4].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.F[C:21]1[C:29]([F:30])=[C:28]([F:31])[C:27]([N+:32]([O-:34])=[O:33])=[CH:26][C:22]=1[C:23]([OH:25])=[O:24]>C1COCC1>[F:30][C:29]1[C:21]([NH:4][C:3]2[CH:5]=[CH:6][C:7]([I:9])=[CH:8][C:2]=2[F:1])=[C:22]([CH:26]=[C:27]([N+:32]([O-:34])=[O:33])[C:28]=1[F:31])[C:23]([OH:25])=[O:24]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 2-fluoro-4-iodoaniline (2.9 g, 11.8 mmoles) in 50 ml anhydrous THF at −60° C., 40 ml of a 1M solution of LHMDS in THF (40 mmoles) is added dropwise. In a separate flask, 2,3,4-trifluoro-5-nitrobenzoic acid (5 g, 22.6 mmoles), previously dissolved in THF (50 ml), is treated, at −60° C., with 25 ml of a 1M solution of LHMDS in THF (25 mmoles). Both solutions are stirred at −78° C. for 45 min and the second solution is transferred via cannula to the first reaction mixture. After completion of the addition the resulting mixture is stirred under argon at room temperature for 15 hours. The reaction mixture is quenched with water, then 1N HCl is added (pH=0-1) followed by brine (100 ml). The crude material is extracted with THF (3×100 ml), the organic layers are combined and dried (Na2SO4) and the solvent is removed to give the title compound.

Workup

additionAfter completion of the addition the resulting mixture
stirringis stirred under argon at room temperature for 15 hours
customThe reaction mixture is quenched with water
addition1N HCl is added (pH=0-1)
extractionThe crude material is extracted with THF (3×100 ml)
dry with materialdried (Na2SO4)
customthe solvent is removed

Sources & evidence

ORD record: ord-4b6e6ca4670347028204acb407a82697
Source dataset: uspto-grants-2010_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07820664B2

Reaction notes

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