3-(Trifluoromethyl)phenol → 2-Chloro-6-[3-(trifluoromethyl)phenoxy]pyridine
Reaction equation
[H-].[Na+].[F:3][C:4]([F:13])([F:12])[C:5]1[CH:6]=[C:7]([OH:11])[CH:8]=[CH:9][CH:10]=1.[Cl:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17](Cl)[N:16]=1>CN(C)C(=O)C>[Cl:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([O:11][C:7]2[CH:8]=[CH:9][CH:10]=[C:5]([C:4]([F:12])([F:13])[F:3])[CH:6]=2)[N:16]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 90 °C
Procedure
17.45 g (690 mmol) of sodium hydride (95 percent) was suspended in 420 ml of N,N-dimethylacetamide. 106.7 g (658 mmol) of 3-(trifluoromethyl)phenol was added dropwise over 2 hours at 15° C. The resultant phenate solution was added dropwise over 2.5 hours, under nitrogen, to a solution of 162.4 g (1.097 mol) of 2,6-dichloropyridine in 330 ml of N,N-dimethylacetamide, heated to 90° C. After a further 3 hours of reaction time, the mixture was cooled to room temperature, the precipitate of sodium chloride was filtered off and the filtrate was concentrated. The residue was taken up with toluene and 0.1 N hydrochloric acid, and the organic phase was washed with saturated sodium chloride solution and concentrated. The oily residue (ca. 200 g) was distilled under a vacuum. The yield of the title compound was 151.5 g (84 percent) of a colorless oil, content (GC) 99.8 percent. Other data concerning the title compound was:
Workup
- customAfter a further 3 hours of reaction time
- temperaturethe mixture was cooled to room temperature
- filtrationthe precipitate of sodium chloride was filtered off
- concentrationthe filtrate was concentrated
- washthe organic phase was washed with saturated sodium chloride solution
- concentrationconcentrated
- distillationThe oily residue (ca. 200 g) was distilled under a vacuum
Sources & evidence
- ORD record
- ord-10dbb508214542b38be7782620b1145f
- Source dataset
- uspto-grants-2003_10
- Patent number
- US06635766B1
Reaction notes
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