3-Fluoroaniline → 2-(3-Fluoro-anilino)-4-methoxybenzoic acid
Reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=[O:8])=[C:5](Cl)[CH:4]=1.C(=O)([O-])[O-].[K+].[K+].[F:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH2:23]>>[F:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH:23][C:5]1[CH:4]=[C:3]([O:2][CH3:1])[CH:11]=[CH:10][C:6]=1[C:7]([OH:9])=[O:8]Participants
Procedure
4-methoxy-2-chloro-benzoic acid (2.0 g), potassium carbonate (1.78 g), 3-fluoroaniline (6.7 mL) and Cu powder (100 mg) were combined and heated at 125 C for 1 h. The reaction was cooled and partitioned between saturated aqueous sodium carbonate and ethyl ether. The aqueous solution was extracted once with ether, then the combined organic solutions were washed with saturated aqueous sodium carbonate (2×). The combined aqueous solutions were acidified to pH 3.5 with conc HCl and extracted with EtOAc (4×). The combined organic solutions were dried (MgSO4) and concentrated. Flash chromatography (0 to 10% MeOH in CH2Cl2) provided a solid, which was recrystallized from CH2Cl2/hexanes to give 1.9 g of 2-(3-fluoro-anilino)-4-methoxybenzoic acid.
Workup
- temperatureheated at 125 C for 1 h
- temperatureThe reaction was cooled
- custompartitioned between saturated aqueous sodium carbonate and ethyl ether
- extractionThe aqueous solution was extracted once with ether
- washthe combined organic solutions were washed with saturated aqueous sodium carbonate (2×)
- extractionextracted with EtOAc (4×)
- dry with materialThe combined organic solutions were dried (MgSO4)
- concentrationconcentrated
- customFlash chromatography (0 to 10% MeOH in CH2Cl2) provided a solid, which
- customwas recrystallized from CH2Cl2/hexanes
Sources & evidence
- ORD record
- ord-e34d3dee419d43209df986bb9538e5b4
- Source dataset
- uspto-grants-2011_03
- Patent number
- US07906521B2
Reaction notes
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