Methallyl alcohol → (5-Methyl-3-o-tolyl-4,5-dihydroisoxazole-5-yl)methanol

HRID 58941

Reaction equation

HRID 58941 reaction equation
[CH3:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[CH:4]=[N:5][OH:6].ClN1C(=O)CCC1=O.C([O-])(O)=O.[Na+].[CH3:24][C:25](=[CH2:28])[CH2:26][OH:27]>ClC(Cl)C.CN(C)C=O>[CH3:24][C:25]1([CH2:26][OH:27])[O:6][N:5]=[C:4]([C:3]2[CH:7]=[CH:8][CH:9]=[CH:10][C:2]=2[CH3:1])[CH2:28]1

Participants

7

Reactant 4

HCID 10557Methallyl alcoholHCID 31398ChlorosuccinimideHCID 1024012-Methyl-benzaldoxime2×HCID 516892Sodium Bicarbonate

Product 1

HCID 90329319(5-Methyl-3-o-tolyl-4,5-dihydroisoxazole-5-yl)methanol

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 63651,1-DichloroethaneSolvent

Procedure

60 g of 2-methylbenzaldehyde oxime was dissolved in 1 L of dichloroethane, and then, 65 g of N-chlorosuccinimide and 100 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 thin layer chromatography (TLC). When 2-methylbenzaldehyde oxime, which was a starting material, disappeared, the reaction mixture was cooled to a temperature of 0° C., and then 56 g of NaHCO3 and 41 mL of 2-methyl-2-propene-1-ol were sequentially added thereto. The reaction mixture was stirred at room temperature overnight, and then washed with water, and then, an separated organic layer was dried and concentrated by using magnesium sulfate, and then, purified by column chromatography to obtain 70 g of (5-methyl-3-o-tolyl-4,5-dihydroisoxazole-5-yl)methanol. The obtained compound was dissolved in 1 L of toluene, and then, 1 L of water, 90 g of NaOH, and 4.5 g of tetrabutylammonium hydrogensulfate were added thereto. After the reaction mixture was stirred for 30 minutes at room temperature, 77 g of 2,6-difluorobenzyl chloride was slowly dropped thereto. The reaction mixture was stirred at a temperature of 60° C. for 5 hours and cooled, and then, a separated organic layer was washed with water and then dried by using magnesium sulfate and concentrated, and the concentrate was separated by silicagel column chromatography to obtain 88 g of 5-((2,6-difluorobenzyloxy)methyl)-5-methyl-3-o-tolyl-4,5-dihydroisoxazole.

Workup

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

Sources & evidence

ORD record
ord-dcc34d63a7ae470584e098f5a0fe670c
Source dataset
uspto-grants-2016_09
Patent number
US09439432B2

Linked notes

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