1,1,1-Trifluoro-2-propanol → 6-Methyl-4-(2,2,2-trifluoro-1-methylethoxy)pyridine-2-carbonitrile

HRID 1880741Notes

Reaction equation

HRID 1880741 reaction equation
[H-].[Na+].[F:3][C:4]([F:9])([F:8])[CH:5]([OH:7])[CH3:6].Cl[C:11]1[CH:16]=[C:15]([CH3:17])[N:14]=[C:13]([C:18]#[N:19])[CH:12]=1.[Cl-].[NH4+]>CN(C)C=O>[CH3:17][C:15]1[N:14]=[C:13]([C:18]#[N:19])[CH:12]=[C:11]([O:7][CH:5]([CH3:6])[C:4]([F:9])([F:8])[F:3])[CH:16]=1

Participants

6

Reactant 4

HCID 97741,1,1-Trifluoro-2-propanolHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 185052494-Chloro-6-methylpyridine-2-carbonitrile

Product 1

HCID 595703936-Methyl-4-(2,2,2-trifluoro-1-methylethoxy)pyridine-2-carbonitrileYield 97.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Into 6 ml of N,N-dimethylformamide was suspended 0.18 g of sodium hydride (60% oily), and 0.44 g of 1,1,1-trifluoro-2-propanol was added at 10° C. After stirring for 10 minutes, 0.49 g of 4-chloro-6-methylpyridine-2-carbonitrile was added, 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. 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 0.72 g of 6-methyl-4-(2,2,2-trifluoro-1-methylethoxy)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
  4. washwashed with an aqueous saturated sodium chloride solution
  5. dry with materialdried with anhydrous magnesium sulfate
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-d1b25b86f1564086a6560e35800a4bc2
Source dataset
uspto-grants-2012_11
Patent number
US08318776B2

Reaction notes

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