Sodium Hydroxide → HCID 57705887, compound

Participants

Reaction Conditions

Reaction Steps

To a cooled solution of 83.20A (0.7036 g, 1.879 mmol) in dry THF (15 mL) at 0° C. was added LAH (1.0 M in THF) (4 mL, 4.0 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 purified by flash chromatography (SiO2 gel 60, eluted with 0%-50% EtOAc in hexanes). Fractions containing the desired product were combined and concentrated to provide a colorless oil that solidified as 83.20B (300.5 mg, 46% yield). 1H NMR (400 MHz, CDCl3) δ ppm 7.16 (1H, s), 7.10 (2H, m), 6.92 (1H, m), 6.77 (1H, dd, J=5.9, 3.1 Hz), 4.74 (2H, s), 3.81 (3H, m), 2.73 (1H, ddd, J=10.3, 8.3, 1.8 Hz), 2.17 (1H, m), 2.04 (1H, m), 1.87 (1H, m), 1.73 (3H, m), 1.42 (1H, m), 0.78 (3H, s), 0.64 (3H, s). Chiral separation of 83.20B was accomplished on Chiracel-OJ (2% IPA in hexane) to provide 83.20C (peak 1) and 83.20D (peak 2). Both enantiomers were used to synthesize example compounds, and both enantiomers gave active compounds.

Provenance & Evidence