Potassium Bicarbonate → 5-(2,6-Difluorophenyl)-N,N-dimethyl-4,5-dihydroisoxazole-3-carboxamide

HRID 1802330Notes

Reaction equation

HRID 1802330 reaction equation
[CH3:1][N:2]([CH3:9])[C:3](=[O:8])[C:4](Cl)=[N:5][OH:6].[F:10][C:11]1[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[C:12]=1[CH:13]=[CH2:14].C(=O)(O)[O-].[K+]>ClC1C=CC=CC=1.O>[F:10][C:11]1[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[C:12]=1[CH:13]1[O:6][N:5]=[C:4]([C:3]([N:2]([CH3:9])[CH3:1])=[O:8])[CH2:14]1

Participants

6

Reactant 3

HCID 516893Potassium BicarbonateHCID 27783002,6-DifluorostyreneHCID 53423335Ethanimidoyl chloride, 2-(dimethylamino)-N-hydroxy-2-oxo-2×

Product 1

HCID 666182295-(2,6-Difluorophenyl)-N,N-dimethyl-4,5-dihydroisoxazole-3-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 7964ChlorobenzeneSolvent

Conditions

Temperature
10 °C

Procedure

To a 1000-mL round bottom flask equipped with a mechanical stirrer, thermometer and addition funnel were added 2-(dimethylamino)-N-hydroxy-2-oxoethanimidoyl chloride (94.0 g, 0.62 mol) and a solution of 2,6-difluorostyrene (84.0 g, 0.60 mol) in chlorobenzene (275 g). The reaction mixture was cooled to 10° C., and then a solution of potassium bicarbonate (70 g, 0.70 mol) in water (350 mL) was added dropwise over 1 h while maintaining the temperature between 10 to 15° C. When gas chromatography analysis of the reaction mixture showed about 3% of 2-(dimethylamino)-N-hydroxy-2-oxo-ethanimidoyl chloride remaining, water (200 mL) was added to the reaction mixture, and the layers were separated. The organic layer was washed with water (300 mL) and concentrated under reduced pressure. Toluene was added to the resulting residue, and the mixture was concentrated under reduced pressure to provide the title compound as an oil (144g).

Workup

  1. customTo a 1000-mL round bottom flask equipped with a mechanical stirrer
  2. additionthermometer and addition funnel
  3. temperaturewhile maintaining the temperature between 10 to 15° C
  4. additionwas added to the reaction mixture
  5. customthe layers were separated
  6. washThe organic layer was washed with water (300 mL)
  7. concentrationconcentrated under reduced pressure
  8. additionToluene was added to the resulting residue
  9. concentrationthe mixture was concentrated under reduced pressure

Sources & evidence

ORD record
ord-74561858295a455ab3d0fd9486582400
Source dataset
uspto-grants-2013_01
Patent number
US08349870B2

Reaction notes

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