Sodium Hydroxide → HCID 11951561, compound

Participants

Reaction Steps

N-(4-fluoro-phenyl)-N-piperidin-4-yl-acetamide (60 mg; 0.25 mmol; 1 eq.), see Example 6 for deprotecting procedure, and bicyclo[3.2.1]octan-8-one (37 mg, 0.3 mmol, 1.2 eq.) were dissolved in dichloromethane (1.5 mL) and DCM (1.5 mL) and treated with Ti(OiPr)4 (213 mg, 0.75 mol, 3 eq.). The reaction was stirred under nitrogen at room temperature for 48 hours, then cooled in a dry ice/isopropanol bath to ˜−40° C. and quenched with methanol (4 mL). The reaction was stirred for 15 minutes at that temperature, then treated with 4.0 eq sodium borohydride (37 mg, 1 mmol). The reaction was slowly warmed to room temperature and stirred for 2 hours. The reaction was then treated with 1 N NaOH (2 mL), stirred vigorously for 30 minutes, filtered through Celite and the solids rinsed with CH2Cl2 (4×5 mL). The filtrates were combined and washed with H2O, saturated brine, dried (Na2SO4) and filtered. The filtrate was concentrated under reduced pressure and the crude product was purified by preparative HPLC (2-99 H2O—CH3CN gradient, 15 minute method) to afford the desired product. LC/MS M/Z 345.3, retention time 2.34 minutes 10-99% CH3CN/H2O gradient with 0.05% TFA.

Provenance & Evidence