Dimethylformamide → 2-Fluoro-6-(2-trifluoromethyl-4-thienyloxy)pyridine

HRID 1793771Notes

Reaction equation

HRID 1793771 reaction equation
F[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[N:3]=1.CN(C=O)C.C([O-])([O-])=O.[K+].[K+].[OH:20][C:21]1[CH:22]=[C:23]([C:26]([F:29])([F:28])[F:27])[S:24][CH:25]=1>O>[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([O:20][C:21]2[CH:22]=[C:23]([C:26]([F:29])([F:28])[F:27])[S:24][CH:25]=2)[N:3]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 739342,6-DifluoropyridineHCID 110842734-Hydroxy-2-(trifluoromethyl)thiophene

Product 1

HCID 121159912-Fluoro-6-(2-trifluoromethyl-4-thienyloxy)pyridineYield 74.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

1.00 g of 2,6-difluoropyridine is introduced into 10 ml of DMF under nitrogen and 1.44 g of K2CO3 are added at RT. 1.61 g of 4-hydroxy-2-trifluoromethylthiophene are added and the mixture is heated at 80° C. for 4 h, then cooled to RT and poured into water. After extraction twice with heptane/ethyl acetate (1:1) and twice with ethyl acetate the product is washed with water and saturated sodium chloride solution, dried over MgSO4 and concentrated. Chromatographic purification on silica gel with heptane/ethyl acetate (3:7) as eluent gives 1.7 g of 2-fluoro-6-(2-trifluoromethyl-4-thienyloxy)pyridine as a colorless oil.

Workup

  1. temperaturecooled to RT
  2. extractionAfter extraction twice with heptane/ethyl acetate (1:1)
  3. washtwice with ethyl acetate the product is washed with water and saturated sodium chloride solution
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customChromatographic purification on silica gel with heptane/ethyl acetate (3:7) as eluent

Sources & evidence

ORD record
ord-cdff3a1fbdba4acca673281e345dd166
Source dataset
uspto-grants-2006_04
Patent number
US07022650B2

Reaction notes

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