反应详情

A solution of 1-(tert-butyloxycarbonyl)-4-piperidinone (20 g, 0.10 mol), 2-amino-5-chlorobenzyl alcohol (17.34 g, 0.11 mol) and acetic acid (14 mL, 0.22 mol) in dry toluene (500 mL) was heated at reflux temperature, with water elimination by means of azeotrope distillation with a Dean-Stark device, for 6 hours. The mixture was then cooled and vacuum concentrated up to half volume. NaBH3CN (20 g, 0.32 mol) and dry THF (300 mL) were added to the resulting solution. Acetic acid (10 mL, 0.17 mol) was then dripped for one hour. The reaction was stirred at room temperature for 24 hours. The mixture was vacuum concentrated and the residue was dissolved in ethyl acetate (750 mL), washed with a NaHCO3-saturated solution (4×250 mL) and a NaCl-saturated solution (250 mL), dried and evaporated to dryness. The residue was purified by means of flash chromatography eluting with a mixture of ethyl acetate:petroleum ether (1:3). The desired product was thus obtained as an oil (32.7 g, 96%).

1. temperatureat reflux temperature
2. distillationwith water elimination by means of azeotrope distillation with a Dean-Stark device
3. temperatureThe mixture was then cooled
4. concentrationvacuum concentrated up to half volume
5. concentrationconcentrated
6. dissolutionthe residue was dissolved in ethyl acetate (750 mL)
7. washwashed with a NaHCO3-saturated solution (4×250 mL)
8. dry with materiala NaCl-saturated solution (250 mL), dried
9. customevaporated to dryness
10. customThe residue was purified by means of flash chromatography
11. washeluting with a mixture of ethyl acetate:petroleum ether (1:3)