A mixture of (F2) (0.020 g, 0.05 mmol), titanium (IV) isopropoxide (0.045 mL, 0.15 mmol) and (1R,4S)-bicyclo[2.2.1]heptan-2-one (3 eq) was stirred at room temperature for 18 h in dichloroethane (0.5 mL). Sodium triacetoxyborohydride (0.011 g, 0.050 mmol) was added and the mixture stirred at room temperature for 1 h. The solvent was evaporated and 6N NaOH (0.5 mL) and methanol (1 mL) was added and then triturated to give a white solid that was washed with methanol (1 mL) and EtOAc (1 mL). The filtrate was concentrated under reduced pressure to afford the crude product which was purified by reverse phase preparative HPLC to afford 1′-(bicyclo[2.2.1]heptan-2-yl)-N-(pentan-3-yl)spiro[indene-1,4′-piperidine]-3-carboxamide (Compound No. 14) (0.013 g). LC/MS (10-90% over 3 min with 0.9% FA) m/z 324.1 (M+1), retention time 2.2 minutes.
