3-Benzyl-3-azabicyclo[3.2.1]octan-8-one

Synthesis

50-00-0

120-92-3

100-46-9

83507-33-9

General procedure for the synthesis of 3-benzyl-3-azabicyclo[3.2.1]octan-8-one (Intermediate I-32) from formaldehyde, cyclopentanone, and benzylamine: In a 2L round-bottomed flask equipped with a condenser tube and nitrogen introduction tube, benzylamine (127 g, 1.2 mol, 1.0 equiv.) and methanol (800 mL) were added, followed by the slow dropwise addition of glacial acetic acid (127 g, 1.2 mol, 1.0 equiv). Intermediate I-31 (100 g, 1.2 mol, 1.0 eq.) and paraformaldehyde (107 g, 3.6 mol, 3.0 eq.) were then added. The reaction mixture was stirred at 80 °C for 3 hours and then continued at room temperature for 18 hours. Upon completion of the reaction, the excess solvent was removed by evaporation and the residue was diluted with ethyl acetate and solid sodium bisulfite (104 g) was added. The crude reaction mixture was continued to be stirred for 1.5 hours and subsequently extracted with ethyl acetate. The organic layers were combined, dried with anhydrous Na2SO4, filtered to remove solids and the filtrate was concentrated by evaporation. The crude product was purified by silica gel column chromatography to afford intermediate I-32 (47.2 g, 18% yield) as a yellow oil.1H-NMR (400 MHz, CDCl3) δ: 7.35 (m, 4H), 7.26 (m, 1H), 3.59 (s, 2H), 2.93 (m, 2H), 2.39 (d, J=10.8 Hz, 2H). 2.50 (m, 2H), 1.93 (m, 2H), 1.81 (m, 2H).MS (ESI): m/z 216.1 (M+H+).

References