1'-benzylspiro[indoline-3,4'-piperidine]

Synthesis

22065-85-6

100-63-0

474538-99-3

1. Preparation of Intermediate Compound 15: To a solution of phenylhydrazine (3.2 mL; 1.1 eq.) dissolved in toluene/acetonitrile (49/1, 50 mL) was slowly added trifluoroacetic acid (16.8 mL; 5 eq.) at room temperature. The reaction mixture was heated to 35 °C. Subsequently, a solution of 1-benzyl-4-piperidinecarboxaldehyde (6 g; 0.03 mol) in toluene/acetonitrile (49/1, 10 mL) was added slowly and dropwise. The reaction mixture was stirred at 35 °C overnight and then cooled to -10 °C. After addition of methanol (7 mL), sodium borohydride (1.7 g; 1.5 eq.) was added in batches. The mixture was continued to stir at room temperature for 1 hour. Upon completion of the reaction, 10% ammonia solution was added and the organic layer was extracted with ethyl acetate, dried over anhydrous magnesium sulfate, filtered and concentrated. The crude product was purified by silica gel column chromatography (75 g SiO2, 35-70 μm; eluent: dichloromethane/methanol 98/2) to afford intermediate compound 15 (3.3 g, 40% yield).

References