2,3,6-Trifluorobenzyl bromide → 4-Methyl-2-[(2,3,6-trifluorobenzyl)oxy]pyridine

HRID 1486318Notes

Reaction equation

HRID 1486318 reaction equation
Br[CH2:2][C:3]1[C:8]([F:9])=[C:7]([F:10])[CH:6]=[CH:5][C:4]=1[F:11].[OH:12][C:13]1[CH:18]=[C:17]([CH3:19])[CH:16]=[CH:15][N:14]=1>C1COCC1.C(=O)([O-])[O-].[Ag+2]>[CH3:19][C:17]1[CH:16]=[CH:15][N:14]=[C:13]([O:12][CH2:2][C:3]2[C:4]([F:11])=[CH:5][CH:6]=[C:7]([F:10])[C:8]=2[F:9])[CH:18]=1

Participants

5

Reactant 2

HCID 5190612,3,6-Trifluorobenzyl bromideHCID 178428601HCID 178428601, compound

Product 1

HCID 1178587044-Methyl-2-[(2,3,6-trifluorobenzyl)oxy]pyridineYield 15.5%

Reagents, catalysts & solvents 2

HCID 178418647HCID 178418647, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 8.32 g (36.96 mmol) of 2-(bromomethyl)-1,3,4-trifluorobenzene and 4.84 g (44.35 mmol) of 2-hydroxy-4-methylpyridine [CAS No.: 13466-41-6] was dissolved in 227 ml of THF. The solution was admixed with 12.23 g (44.35 mmol) of silver carbonate and the mixture was heated to reflux with exclusion of light overnight. Subsequently, the reaction mixture was filtered through kieselguhr and washed with ethyl acetate, and the filtrate was concentrated. The crude product was purified by means of silica gel chromatography (eluent:cyclohexane/dichloromethane gradient: 10/0 to 1/1). 1.45 g of the title compound were obtained (15% of theory).

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux with exclusion of light overnight
  3. filtrationSubsequently, the reaction mixture was filtered through kieselguhr
  4. washwashed with ethyl acetate
  5. concentrationthe filtrate was concentrated
  6. customThe crude product was purified by means of silica gel chromatography (eluent:cyclohexane/dichloromethane gradient: 10/0 to 1/1)

Sources & evidence

ORD record
ord-ff84e7bf7a3b4bceab4a0a42840af124
Source dataset
uspto-grants-2016_08
Patent number
US09422285B2

Reaction notes

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