Water → 2-(3-Bromo-5-fluorophenoxy)-5-(trifluoromethyl)-pyridine
Reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([OH:9])[CH:5]=[C:6]([F:8])[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].Cl[C:17]1[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][N:18]=1.O>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]([CH:5]=[C:6]([F:8])[CH:7]=1)[O:9][C:17]1[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][N:18]=1Participants
Procedure
To a solution of 3-bromo-5-fluorophenol (2.54 g, 0.013 mol) in DMF (12 mL) under a N2 atmosphere was added potassium carbonate (3.59 g, 0.026 mol) and the reaction was stirred for 20 min at RT. 2-Chloro-5-trifluoromethylpyridine (2.4 g, 0.013 mol) was added and the reaction mixture was refluxed at 110° C. overnight. Water was added and the mixture was extracted with ethyl acetate three times. The organic layer was washed with brine, dried over Na2SO4 and evaporated to dryness. The residue was purified by silica gel column chromatography (10% ethyl acetate in hexane) to give the title compound (4.28 g, 96%). 1H NMR (500 MHz, CDCl3): δ 8.45 (s, 1H), 7.96 (dd, J=2 Hz, J=8.5 Hz, 1H), 7.16-7.15 (m, 2H), 7.08 (d, J=8.5 Hz, 1H), 6.89-6.85 (m, 1H); m/z (337.9, M+ H+)
Workup
- temperaturethe reaction mixture was refluxed at 110° C. overnight
- extractionthe mixture was extracted with ethyl acetate three times
- washThe organic layer was washed with brine
- dry with materialdried over Na2SO4
- customevaporated to dryness
- customThe residue was purified by silica gel column chromatography (10% ethyl acetate in hexane)
Sources & evidence
- ORD record
- ord-11bdcb2f5ad64ddab35d39656aae9754
- Source dataset
- uspto-grants-2011_10
- Patent number
- US08044052B2
Reaction notes
Loading…