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

HRID 1916438Notes

Reaction equation

HRID 1916438 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

A 1000-mL round bottom flask equipped with a mechanical stirrer, thermometer and addition funnel was charged with 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 a solution of potassium bicarbonate (70 g, 0.70 mol) in water (350 mL) was added dropwise over 1 h while maintaining the reaction 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. The layers were separated, and the organic layer was washed with water (300 mL) and concentrated under reduced pressure. Toluene was added to the resulting residu, and the mixture was again concentrated under reduced pressure to provide the title compound as an oil (144 g).

Workup

  1. customA 1000-mL round bottom flask equipped with a mechanical stirrer
  2. additionthermometer and addition funnel
  3. temperaturewhile maintaining the reaction 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 residu
  9. concentrationthe mixture was again concentrated under reduced pressure

Sources & evidence

ORD record
ord-72fa758374f64d6dbecedc80bf3c82f3
Source dataset
uspto-grants-2013_12
Patent number
US08618137B2

Reaction notes

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