Sodium hydride → 4-(2,2-Difluoropropoxyl)pyrimidine-5-carbonitrile

HRID 1749450Notes

Reaction equation

HRID 1749450 reaction equation
[H-].[Na+].[F:3][C:4]([F:8])([CH3:7])[CH2:5][OH:6].Cl[C:10]1[C:15]([C:16]#[N:17])=[CH:14][N:13]=[CH:12][N:11]=1>C1COCC1>[F:3][C:4]([F:8])([CH3:7])[CH2:5][O:6][C:10]1[C:15]([C:16]#[N:17])=[CH:14][N:13]=[CH:12][N:11]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 131269094-Chloropyrimidine-5-carbonitrileHCID 133948182,2-Difluoropropanol

Product 1

HCID 1181620714-(2,2-Difluoropropoxyl)pyrimidine-5-carbonitrileYield 59.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of sodium hydride (60% dispersed in mineral oil, 315 mg, 7.88 mmol) in THF (20 mL) was added 2,2-difluoropropan-1-ol (757 mg, 7.88 mmol) at 0° C. and the resulting mixture was stirred for 1 h. Then 4-chloropyrimidine-5-carbonitrile (1.00 g, 7.16 mmol) was added in portions and the mixture was stirred at room temperature for 30 min. The reaction was quenched with saturated aqueous ammonium chloride solution and extracted with ethyl acetate (500 mL×2). The combined organic layers were dried and concentrated and the residue was purified by silica gel chromatography column (12% ethyl acetate in petroleum ether) to afford the title compound (850 mg, 4.27 mmol, 58% yield) as a yellow solid. MS (ESI) m/z 200.0 [M+H]+.

Workup

  1. stirringthe mixture was stirred at room temperature for 30 min
  2. customThe reaction was quenched with saturated aqueous ammonium chloride solution
  3. extractionextracted with ethyl acetate (500 mL×2)
  4. customThe combined organic layers were dried
  5. concentrationconcentrated
  6. customthe residue was purified by silica gel chromatography column (12% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-5849baf05ad74c56b8805592a567beb9
Source dataset
uspto-grants-2015_10
Patent number
US09156798B2

Reaction notes

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