2,2,2-Trifluoroethanol → 6-Methyl-4-(2,2,2-trifluoroethoxy)pyridine-2-carbonitrile

HRID 1880739Notes

Reaction equation

HRID 1880739 reaction equation
[H-].[Na+].[F:3][C:4]([F:8])([F:7])[CH2:5][OH:6].Cl[C:10]1[CH:15]=[C:14]([CH3:16])[N:13]=[C:12]([C:17]#[N:18])[CH:11]=1.[Cl-].[NH4+]>CN(C)C=O>[CH3:16][C:14]1[N:13]=[C:12]([C:17]#[N:18])[CH:11]=[C:10]([O:6][CH2:5][C:4]([F:8])([F:7])[F:3])[CH:15]=1

Participants

6

Reactant 4

HCID 64092,2,2-TrifluoroethanolHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 185052494-Chloro-6-methylpyridine-2-carbonitrile

Product 1

HCID 595703876-Methyl-4-(2,2,2-trifluoroethoxy)pyridine-2-carbonitrileYield 92.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Into 8 ml of N,N-dimethylformamide was suspended 0.22 g of sodium hydride (60% oily), and 0.47 g of trifluoroethyl alcohol was added at 10° C. After stirring for 10 minutes, 0.6 g of 4-chloro-6-methylpyridine-2-carbonitrile was added at 0° C., the mixture was stirred for 1 hour, and the reaction solution was poured into an aqueous saturated ammonium chloride solution, followed by extraction with tert-butyl=methyl=ether three times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution, dried with anhydrous magnesium sulfate, and concentrated. The residue was subjected to silica gel column chromatography to obtain 0.79 g of 6-methyl-4-(2,2,2-trifluoroethoxy)pyridine-2-carbonitrile.

Workup

  1. additionwas added at 10° C
  2. stirringthe mixture was stirred for 1 hour
  3. extractionfollowed by extraction with tert-butyl=methyl=ether three times
  4. washwashed with an aqueous saturated sodium chloride solution
  5. dry with materialdried with anhydrous magnesium sulfate
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-80498211824f4b7bb03a2ec75f563384
Source dataset
uspto-grants-2012_11
Patent number
US08318776B2

Reaction notes

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