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

HRID 75168Notes

Reaction equation

HRID 75168 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-carboxamideYield 94.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 7964ChlorobenzeneSolvent

Conditions

Temperature
10 °C

Procedure

To a 1 L round bottom flask equipped with a mechanical stirrer, thermometer and addition funnel was added 2-(dimethylamino)-N-hydroxy-2-oxoethanimidoyl chloride (94.0 g, 0.62 mol) and 2,6-difluorostyrene (84.0 g, 0.60 mol) in chlorobenzene (275 g). The reaction mixture was cooled to 10° C., and then potassium bicarbonate (70 g, 0.70 mol) in water (350 mL) was added dropwise over 1 h while maintaining the temperature between 10 and 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 (144 g).

Workup

  1. customTo a 1 L round bottom flask equipped with a mechanical stirrer
  2. additionthermometer and addition funnel
  3. temperaturewhile maintaining the temperature between 10 and 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-2f2a20fbde1a40679f120ebea0a733d7
Source dataset
uspto-grants-2014_09
Patent number
US08835427B2

Reaction notes

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