3-(Trifluoromethyl)phenol → 4-Methyl-2,3,5-trifluoro-6-(3-trifluoromethylphenoxy)pyridine
Reaction equation
[F:1][C:2]([F:11])([F:10])[C:3]1[CH:4]=[C:5]([OH:9])[CH:6]=[CH:7][CH:8]=1.[H-].[Na+].[CH3:14][C:15]1[C:20]([F:21])=[C:19](F)[N:18]=[C:17]([F:23])[C:16]=1[F:24]>CN(C=O)C.C(#N)C>[CH3:14][C:15]1[C:20]([F:21])=[C:19]([O:9][C:5]2[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:10])([F:11])[F:1])[CH:4]=2)[N:18]=[C:17]([F:23])[C:16]=1[F:24]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 75 °C
Procedure
To a solution of 3-trifluoromethyl phenol (13.2 ml, 0.11 mol) in anhydrous DMF (200 ml) is added sodium hydride (4.8 g, 60%, 0.12 mol). After 30 min at ambient temperature the solution is added to another solution of 4-methyl-2,3,5,6-tetrafluoropyridine (16.5 g, 0.1 mol) in anhydrous acetonitrile (700 ml) at 50° C. during 3 hours. The resulting mixture is then stirred for 1 hour at 50° C. and 16 hours at 75° C. The solvents are removed in vacuo and to the residue is added ethyl acetate/pentane (1000 ml, 1/1 by volume). The mixture is washed twice with 2 M NaOH and 5 times with water. After drying and evaporation of the organic layer, the residue is purified by vacuum destillation. One obtains a colorless oil (23.3 g, 76 mmol, 76% yield, bp. 76° C. at 0.025 mbar) of 4-methyl-2,3,5-trifluoro-6-(3-trifluoromethylphenoxy)pyridine.
Workup
- customThe solvents are removed in vacuo and to the residue
- additionis added ethyl acetate/pentane (1000 ml, 1/1 by volume)
- washThe mixture is washed twice with 2 M NaOH and 5 times with water
- customAfter drying
- customevaporation of the organic layer
- customthe residue is purified by vacuum destillation
Sources & evidence
- ORD record
- ord-28bd6fd8d0bd42669265c5e30fc07526
- Source dataset
- uspto-grants-2001_10
- Patent number
- US06310006B1
Reaction notes
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