Water → 3-Fluoro-4-(2-methyl-imidazol-1-yl)-benzoic acid

HRID 68785Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][C:12]=1F)[C:5]([O:7]CC)=[O:6].[CH3:14][C:15]1[NH:16][CH:17]=[CH:18][N:19]=1.C([O-])([O-])=O.[K+].[K+].O>CN(C)C=O.C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][C:12]=1[N:16]1[CH:17]=[CH:18][N:19]=[C:15]1[CH3:14])[C:5]([OH:7])=[O:6]

Participants

Conditions

Temperature: 140 °C

Procedure

To a solution of ethyl 3,4-difluorobenzoate (1.5 g) in N,N-dimethylformamide (12 mL) is added 2-methylimidazole (1.3 g) and K2CO3 (2.2 g) and the mixture is heated at 140° C. in a microwave oven for 1 h. After cooling to room temperature, water and ethyl acetate are added and the organic layer is dried (MgSO4) and concentrated. The residue is purified by chromatography (ethyl acetate/hexane 0:1→1:0). The ester is dissolved in methanol (30 mL) and 4 M aqueous NaOH (3 mL) is added and the mixture is stirred at room temperature for 1 h. The mixture is neutralized with 6 M aqueous HCl, concentrated and then acidified with 6 M aqueous HCl. The precipitate is filtered off washing with a small amount of water and dried by suction to give the title compound.

Workup

temperatureAfter cooling to room temperature
dry with materialthe organic layer is dried (MgSO4)
concentrationconcentrated
customThe residue is purified by chromatography (ethyl acetate/hexane 0:1→1:0)
dissolutionThe ester is dissolved in methanol (30 mL)
addition4 M aqueous NaOH (3 mL) is added
concentrationconcentrated
filtrationThe precipitate is filtered off
washwashing with a small amount of water
customdried by suction

Sources & evidence

ORD record: ord-deb8ec60340949e7bc539a82bad5e769
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08822471B2

Reaction notes

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