Chlorosuccinimide → 5-((2,6-Difluorobenzyloxy)methyl)-5-methyl-3-(2-(trifluoromethyl)phenyl)-4,5-dihydroisoxazole

HRID 58945Notes

Reaction equation

HRID 58945 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:11]=[CH:10][CH:9]=[CH:8][C:4]=1[CH:5]=[N:6][OH:7].ClN1C(=O)CCC1=O.C([O-])(O)=O.[Na+].[F:27][C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([F:34])[C:29]=1[CH2:35][O:36][CH2:37][C:38]([CH3:40])=[CH2:39]>ClCCCl.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.ClCCl.CN(C)C=O>[F:27][C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([F:34])[C:29]=1[CH2:35][O:36][CH2:37][C:38]1([CH3:40])[O:7][N:6]=[C:5]([C:4]2[CH:8]=[CH:9][CH:10]=[CH:11][C:3]=2[C:2]([F:12])([F:13])[F:1])[CH2:39]1

Participants

9

Reactant 4

HCID 31398ChlorosuccinimideHCID 516892Sodium BicarbonateHCID 16173382-(Trifluoromethyl)benzenecarbaldehyde oximeHCID 112640711,3-Difluoro-2-((2-methylallyloxy)methyl)benzene

Product 1

HCID 894918555-((2,6-Difluorobenzyloxy)methyl)-5-methyl-3-(2-(trifluoromethyl)phenyl)-4,5-dihydroisoxazoleYield 90.2%

Reagents, catalysts & solvents 4

HCID 67553Tetrabutylammonium IodideCatalystHCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

223 mg of 2-trifluoromethylbenzaldehyde oxime was dissolved in 4 mL of 1,2-dichloroethane, and then, 230 mg of N-chlorosuccinimide and 0.4 mL of dimethylformamide were slowly added thereto at a temperature of 0° C. The reaction mixture was stirred at room temperature for 1 hour, and then, the reaction state was confirmed by TLC. When the oxime, which was a starting material, disappeared, the reaction mixture was cooled to a temperature 0° C., and then, 182 mg of NaHCO3, 27 mg of tetrabutylammonium iodide, and 342 mg of 1,3-difluoro-2-((2-methylallyloxy)methyl)benzene were sequentially, slowly added thereto. The reaction mixture was stirred at room temperature overnight, and then, diluted with dichloromethane, and then, washed with water, and the obtained organic layer was dried by using magnesium sulfate and concentrated, and the concentrate was separated by silicagel column chromatography to obtain 410 mg of 5-((2,6-difluorobenzyloxy)methyl)-5-methyl-3-(2-(trifluoromethyl)phenyl)-4,5-dihydroisoxazole.

Workup

  1. customat a temperature of 0° C
  2. temperaturethe reaction mixture was cooled to a temperature 0° C.
  3. additionslowly added
  4. stirringThe reaction mixture was stirred at room temperature overnight
  5. washwashed with water
  6. customthe obtained organic layer was dried
  7. concentrationconcentrated
  8. customthe concentrate was separated by silicagel column chromatography

Sources & evidence

ORD record
ord-9c97f89873f34a5c9abe1bf60c7ee372
Source dataset
uspto-grants-2016_09
Patent number
US09439432B2

Reaction notes

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