4-Fluorophenol → Methyl 4-[[2-(4-fluorophenoxy)-4,6-bis(trifluoromethyl)benzoyl]amino]benzoate
Reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.F[C:10]1[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[C:25]([C:33]([F:36])([F:35])[F:34])[C:11]=1[C:12]([NH:14][C:15]1[CH:24]=[CH:23][C:18]([C:19]([O:21][CH3:22])=[O:20])=[CH:17][CH:16]=1)=[O:13].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:10]2[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[C:25]([C:33]([F:34])([F:35])[F:36])[C:11]=2[C:12]([NH:14][C:15]2[CH:16]=[CH:17][C:18]([C:19]([O:21][CH3:22])=[O:20])=[CH:23][CH:24]=2)=[O:13])=[CH:4][CH:3]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 90 °C
Procedure
4-Fluorophenol (12.05 mg, 0.1075 mmol), methyl 4-[[2-fluoro-4,6-bis(trifluoromethyl)benzoyl]amino]benzoate (40 mg, 0.09774 mmol), and K2CO3 (40.52 mg, 0.29 mmol) were combined in DMF (0.5 mL) and heated at 90° C. for 10 min resulting in complete conversion to methyl 4-[[2-(4-fluorophenoxy)-4,6-bis(trifluoromethyl)benzoyl]amino]benzoate. NaOH (97.73 μL of 3 M, 0.29 mmol) was added and the reaction heated at 90° C. for 2 hours, then at 50° C. for overnight. Additional NaOH was added [2×NaOH (97.73 μL of 3 M, 0.29 mmol), 6 eq] and the reaction heated at 90° C. for 5 hours. HPLC purification using a gradient of acetonitrile in water (10-99%) with 5 mM HCl as a modifier provided 4-(2-(4-fluorophenoxy)-4,6-bis(trifluoromethyl)benzamido)benzoic acid (11) as a white solid. ESI-MS m/z calc. 487.06, found 488.3 (M+1)+; Retention time: 1.84 minutes (3 minutes run). 1H NMR (400 MHz, DMSO-d6) δ 12.83 (s, 1H), 11.14 (s, 1H), 7.99 (s, 1H), 7.94 (d, J=8.7 Hz, 2H), 7.73 (d, J=8.7 Hz, 2H), 7.48 (s, 1H), 7.36-7.22 (m, 4H) ppm.
Sources & evidence
- ORD record
- ord-990d74e180ee40a785e0e4fa9d72b971
- Source dataset
- uspto-grants-2015_08
- Patent number
- US09108903B2
Reaction notes
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