Sodium hydride → 6-Chloro-2-(2,2-difluoro-ethoxy)-nicotinamide

HRID 1664428Notes

Reaction equation

HRID 1664428 reaction equation
[F:1][CH:2]([F:5])[CH2:3][OH:4].[H-].[Na+].Cl[C:9]1[N:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:10]=1[C:11]([NH2:13])=[O:12]>COCCOC.CN(C)C=O.O>[Cl:18][C:16]1[CH:15]=[CH:14][C:10]([C:11]([NH2:13])=[O:12])=[C:9]([O:4][CH2:3][CH:2]([F:5])[F:1])[N:17]=1

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 1361872,2-Difluoroethan-1-olHCID 221427782,6-Dichloropyridine-3-carboxamide

Product 1

HCID 579690086-Chloro-2-(2,2-difluoro-ethoxy)-nicotinamideYield 97.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

2,2-Difluoroethanol (3.51 mL, 55.5 mmol) was added dropwise over 30 minutes to a suspension of NaH (2.22 g, 60% w/w dispersion in oil) in 1,2-dimethoxyethane (40.0 mL) at 14° C. and stirred for 1 hour. A portion of this solution (25 mL, 35 mmol) was added dropwise over 10 minutes to a solution of 2,6-dichloro-nicotinamide (5.30 g, 27.7 mmol) in dimethylformamide (40 mL) at 14° C. The resultant suspension was stirred for an additional 1 hour at 14° C., diluted with water (600 mL) and extracted with EtOAc (3×400 mL). The organic extracts were combined, dried over Na2SO4, filtered and concentrated to give title compound as a light orange solid (6.39 g, 97%). This was used without further purification.

Workup

  1. extractionextracted with EtOAc (3×400 mL)
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-ef2edfc5df2c412292041b07bcdd5b50
Source dataset
uspto-grants-2011_10
Patent number
US08039450B2

Reaction notes

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