Boron trifluoride etherate → HCID 68210982, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of tert-butyl[(2R,3S)-5-oxo-2-(2,5-difluorophenyl)tetrahydro-2H-pyran-3-yl]carbamate (Intermediate 2 in U.S. Pat. No. 7,678,905, the contents of which are herein incorporated by reference in their entirety) (6 g, 18.3 mmol) in DCM (185 mL) cooled to −78° C. was added boron trifluoride diethyl etherate (9.3 mL, 73.3 mmol) dropwise via syringe. After stirring 10 min at −78° C., trimethylsilyldiazomethane (11 mL, 22 mmol, 2 M in hexane) was added dropwise via syringe and the reaction was stirred 1.5 h at −78° C. The reaction mixture was diluted with diethyl ether and sat. aqueous NaHCO3, extracted with diethyl ether (×2) and the combined extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The resulting oil was dissolved in a mixture of DCM (50 mL) and methanol (50 mL) and pyridiniump-toluenesulfonate (460 mg, 1.83 mmol) was added. The reaction was stirred 18 h at rt, then diluted with DCM and sat. aq. NaHCO3, washed with sat. aq. NaHCO3 and brine, then dried over Na2SO4, filtered and concentrated. The resulting oil was purified by column chromatography (100 g column, 8% to 70% EtOAc:Hex ramp) to provide the title compound as a white solid.

Provenance & Evidence