Hydrochloric Acid → HCID 178504132, compound

Temperature

130 °C

Concentrated hydrochloric acid (36% by weight) (3.0 ml, 36 mmol) was added to a solution of 3-hydroxymethyl-1-methyl-4-trifluoromethyl-1H-pyrazole (1.34 g, 7.4 mmol) and thiourea (836 mg, 11 mmol) in 1,4-dioxane (5 ml) and water (2 ml). The mixture was heated in a sealed vessel in the microwave at 130° C. for 10 minutes, cooled to room temperature and potassium carbonate (4.14 g, 30 mmol) dissolved in water (5 ml) was added. 3-Methanesulfonyl-5,5-dimethyl-4,5-dihydroisoxazole (2.12 g, 12 mmol) and 1,4-dioxane (5 ml) were added and the mixture was heated in a sealed vessel in the microwave at 150° C. for 30 minutes. More potassium carbonate (1.38 g, 10 mmol) was added and the mixture was heated in a sealed vessel in the microwave at 150° C. for 20 minutes. The mixture was cooled to room temperature, extracted with ethyl acetate (3×50 ml), the extract dried over magnesium sulfate and concentrated. The residue was purified using preparative HPLC on silica gel (eluent: dichloromethane/ethyl acetate) to give the product as a white solid (220 mg, 10% yield). 1H-NMR (400 MHz, CDCl3): 1.42 (6H, s, Me), 2.84 (2H, s, CH2), 3.89 (3H, s, Me), 4.36 (2H, s, CH2), 7.60 (1H, s, CH).

1. temperaturecooled to room temperature
2. additionwas added
3. temperaturethe mixture was heated in a sealed vessel in the microwave at 150° C. for 30 minutes
4. temperaturethe mixture was heated in a sealed vessel in the microwave at 150° C. for 20 minutes
5. temperatureThe mixture was cooled to room temperature
6. extractionextracted with ethyl acetate (3×50 ml)
7. dry with materialthe extract dried over magnesium sulfate
8. concentrationconcentrated
9. customThe residue was purified

ORD record

ord-a217bca58b40468cb70102fa9e43cca6

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08680290B2