Boron trifluoride etherate → (1S*,2R*)-2-[1-(Tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl]cyclopentanol

To a solution of 1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole (3.04 g, 20.0 mmol) in THF (30 mL), n-butyl lithium (1.63 M solution in hexane; 12.7 mL, 20.7 mmol) was added dropwise at −78° C. for 7 minutes. The reaction solution was stirred for 30 minutes, and boron trifluoride-ethyl ether (3.14 mL, 25.0 mmol) was then added thereto. The reaction solution was further stirred for 10 minutes. Then, cyclopentene oxide (2.08 mL, 24.0 mmol) was added thereto, and the reaction solution was stirred at −78° C. for 3 hours. To the reaction solution, a saturated aqueous solution of sodium hydrogencarbonate (15 mL) was added, followed by extraction four times with ethyl acetate (20 mL). The thus obtained organic layer was dried over anhydrous sodium sulfate. After vacuum concentration, the residue was purified with silica gel chromatography (hexane/ethyl acetate=1:4) to yield the title compound (1.54 g, 33%) in the form of a diastereomeric mixture as a colorless oil.

1. stirringThe reaction solution was further stirred for 10 minutes
2. stirringthe reaction solution was stirred at −78° C. for 3 hours
3. extractionfollowed by extraction four times with ethyl acetate (20 mL)
4. dry with materialThe thus obtained organic layer was dried over anhydrous sodium sulfate
5. concentrationAfter vacuum concentration
6. customthe residue was purified with silica gel chromatography (hexane/ethyl acetate=1:4)

ORD record

ord-18fbd6399661413d8beb367b916ad09c

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08889741B2