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

Participants

Reaction Steps

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.

Provenance & Evidence