Sodium Hydroxide → (5'-(Difluoromethyl)-2-(2,2-dimethylcyclopentyl)-2'-fluoro-1,1'-biphenyl-4-yl)methanol

Participants

Reaction Conditions

Reaction Steps

To a cooled solution of 66.51A (0.8631 g, 2.293 mmol) in dry THF (15.4 mL) at 0° C. was added LAH (1.0 M in THF) (4.6 mL, 4.6 mmol) dropwise. Upon complete addition, the reaction was maintained at 0° C. and was monitored by TLC and LCMS. After 45 minutes, 1N NaOH was added to quench the reaction (gas evolution occurred). The resulting solution was extracted three times with EtOAc. After drying over anhydrous magnesium sulfate, filtration, and concentration, the residue was then purified by flash chromatography (SiO2 gel 60, eluted with 0%-100% EtOAc in hexanes). Fractions containing the desired product were combined and concentrated to a colorless oil as 66.51B (617.1 mg, 77% yield). MS ESI (pos.) m/e: 331.0 (M−H2O)+. Chiral separation of 66.51B was accomplished on a Chiracel-OD column (4% IPA in hexane) to provide 66.51C (peak 1) and 66.51D (peak 2). Both enantiomers were used to synthesize example compounds, and both enantiomers gave active compounds.

Provenance & Evidence