Hydrochloric Acid → HCID 68489986, compound

Temperature

-78 °C

A mixture of pyrazole (14.3 g, 0.21 mmol), 3,4-dihydro-2H-pyrane (29 mL, 0.32 mmol) and trifluoroacetic acid (0.1 mL, 0.0013 mmol) was heated under reflux for 5 hours. After the mixture was cooled to room temperature, sodium hydride (60%, 0.2 g, 0.008 mmol) was added thereto, and the mixture was stirred for 10 minutes. The reaction mixture was subjected to distillation under reduced pressure (60-65° C., 0.5-1 mmHg), whereby 1-(tetrahydropyran-2-yl)-1H-pyrazole (30.8 g, 96%) was obtained. To a stirred solution of the obtained 1-(tetrahydropyran-2-yl)-1H-pyrazole (30 g, 197 mmol) in THF (197 mL), n-butyl lithium (2.6 M hexane solution, 79 mL) was added at −78° C., and the reaction solution was stirred at −78° C. for 30 minutes. To the reaction solution, triisopropyl borate (50.0 mL, 217 mmol) was added at −78° C., and the solution was stirred for 1 hour. To the reaction solution, 2 N hydrochloric acid (200 mL) was added, and the solution was stirred at room temperature for 30 minutes. The solution was extracted three times with chloroform-ethanol. The extracted organic layer was washed sequentially with water and saturated brine and then dried over magnesium sulfate. After the drying agent was removed by filtration, the solvent was evaporated under reduced pressure. The residue was crystallized from ethyl acetate-hexane, whereby the objective compound (16.0 g, 41.4%) was obtained as a colorless solid.

1. stirringthe solution was stirred for 1 hour
2. stirringthe solution was stirred at room temperature for 30 minutes
3. extractionThe solution was extracted three times with chloroform-ethanol
4. washThe extracted organic layer was washed sequentially with water and saturated brine
5. dry with materialdried over magnesium sulfate
6. customAfter the drying agent was removed by filtration
7. customthe solvent was evaporated under reduced pressure
8. customThe residue was crystallized from ethyl acetate-hexane, whereby the objective compound (16.0 g, 41.4%)
9. customwas obtained as a colorless solid

ORD record

ord-1f8a0f632d1d4048823c84ce6b4fb60b

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08314094B2