Water → N-(2-chloro-5-fluoropyridin-3-yl)-2-methylacrylamide

HRID 385593Notes

Reaction equation

HRID 385593 reaction equation
[Cl:1][C:2]1[C:7]([NH2:8])=[CH:6][C:5]([F:9])=[CH:4][N:3]=1.O.[C:11](OCC)(=[O:13])C.N1[CH:22]=[CH:21][CH:20]=CC=1>CC(=C)C(Cl)=O>[Cl:1][C:2]1[C:7]([NH:8][C:11](=[O:13])[C:21]([CH3:20])=[CH2:22])=[CH:6][C:5]([F:9])=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 1049PyridineHCID 8857Ethyl AcetateHCID 447548682-Chloro-5-fluoropyridin-3-amine

Product 1

HCID 57815236N-(2-chloro-5-fluoropyridin-3-yl)-2-methylacrylamide

Reagents, catalysts & solvents 1

HCID 13528Methacryloyl chlorideSolvent

Procedure

To a solution of 1.2 g of 2-chloro-5-fluoropyridin-3-amine in 5 mL of pyridine, 0.86 mL of 2-methylacryloyl chloride was added under cooling with ice, and the mixture was stirred at room temperature for 30 minutes. To the reaction mixture, water and ethyl acetate were added, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, the resultant solution was washed sequentially with water and a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The resultant residue was purified by flash silica gel column chromatography using gradient elution with hexane:ethyl acetate=100:0 to 50:50 to obtain 1.1 g of N-(2-chloro-5-fluoropyridin-3-yl)-2-methylacrylamide as a colorless oily substance.

Workup

  1. temperatureunder cooling with ice
  2. customthe organic layer was separated
  3. extractionthe aqueous layer was extracted with ethyl acetate
  4. washthe resultant solution was washed sequentially with water
  5. dry with materiala saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate
  6. distillationthe solvent was distilled off under reduced pressure
  7. customThe resultant residue was purified by flash silica gel column chromatography
  8. washelution with hexane

Sources & evidence

ORD record
ord-77d63505f368418782c6ce99173f7ae3
Source dataset
uspto-grants-2013_02
Patent number
US08367831B2

Reaction notes

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