Hydrochloric Acid → Isoxazole, 3-[[(2,6-difluorophenyl)methyl]thio]-4,5-dihydro-5,5-dimethyl-

Temperature

140 °C

2,6-Difluorobenzyl alcohol (0.2 ml, 1.8 mmol), thiourea (165 mg, 2.2 mmol), aqueous hydrochloric acid (2M) (2.7 ml) and 1,4-dioxane (3 ml) were mixed and the mixture heated in a sealed vessel in the microwave at 140° C. for 10 minutes. Potassium carbonate (1.1 g, 8 mmol) and 3-methanesulfonyl-5,5-dimethyl-4,5-dihydroisoxazole (380 mg, 2.1 mmol) were added and the mixture was stirred in an open vessel for 10 minutes. The mixture was heated in a sealed vessel in the microwave at 150° C. for 10 minutes. The mixture was diluted with water and extracted with ethyl acetate. The organic extract was washed with water, dried over magnesium sulfate and concentrated. The crude material was purified by chromatography on silica gel (eluent: ethyl acetate/hexane) to give the product as a white solid (120 mg, 26% yield). M.p. 85-87° C. 1H-NMR (400 MHz, CDCl3): 1.43 (6H, s, Me), 2.82 (2H, s, CH2), 4.36 (2H, s, CH2), 6.90 (2H, d, CH), 7.26 (1H, t, CH).

1. temperatureThe mixture was heated in a sealed vessel in the microwave at 150° C. for 10 minutes
2. extractionextracted with ethyl acetate
3. extractionThe organic extract
4. washwas washed with water
5. dry with materialdried over magnesium sulfate
6. concentrationconcentrated
7. customThe crude material was purified by chromatography on silica gel (eluent: ethyl acetate/hexane)

ORD record

ord-ad87b5f6862149629b235e233ef3f8d0

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08680290B2