94994-15-7

18720-35-9

541-41-3

94994-15-7

General procedure: synthesis of intermediate A51I: methyl 4-(hydroxymethyl)bicyclo[2.2.2]octane-1-carboxylate. Intermediate A51A (1.0531 g, 4.96 mmol) was dissolved in THF (40 mL) at 0 °C, and a THF (2 mL) solution of triethylamine (TEA, 1.729 mL, 12.40 mmol) and ethyl chloroformate (1.131 g, 10.42 mmol) was slowly added. The reaction mixture gradually formed a suspension (Et3N-HCl salt). Stirring was continued at 0 °C for 30 min. The suspension was subsequently filtered and the filter cake was washed with THF. The filtrate was slowly added to a suspension of sodium borohydride (0.751 g, 19.85 mmol) in water (2 mL) at 0 °C. The reaction mixture was transferred to room temperature and stirred for 1 hour. Upon completion of the reaction, liquid-liquid partitioning was performed with EtOAc and water. The organic layer was sequentially washed with brine, dried over anhydrous Na2SO4, filtered and concentrated. The crude product was purified by silica gel column chromatography (40 g REDISEP column, eluent 10-50% EtOAc in hexane solution). The fraction containing the target product was collected and concentrated to give the intermediate A51I (0.9 g, 91% yield). Mass spectrum (ES): m/z = 199 [M + H]+; 1H NMR (400 MHz, chloroform-d) δ ppm 3.66 (s, 3H), 3.30 (s, 2H), 1.91-1.73 (m, 6H), 1.52-1.41 (m, 6H).