反应详情

温度

0 °C

Sodium hydride (0.912 g, 23 mmol, 60% oil disp.) which had been rinsed with hexanes (3×10 mL), and dry N,N-dimethylformamide (50 mL) were cooled to 0° C. with stirring under a nitrogen atmosphere. A solution of 1-t-butyloxycarbonyl-4-hydroxyethylpiperidine (4.3 g, 19 mmol) in dry DMF (15 mL) was added, and the mixture stirred for 1 hour. 3-Phenylpropargyl chloride (2.8 g, 19 mmol) was added, and the mixture was heated to reflux for 24 hours. After cooling, the solvent was removed by distillation under reduced pressure. The residue was dissolved in ethyl acetate and extracted with water (3×100 mL), brine (100 mL), dried (MgSO4), filtered, and concentrated under reduced pressure. The crude product was purified by chromatography on silica gel, eluting with 5% ethyl acetate in hexanes, and concentrated under reduced pressure to yield 1-t-butyloxycarbonyl-4-[(3-phenyl-2-propynyloxy)ethyl]piperidine (1.02 g, 16%) as a dark oil. 1H NMR (300 MHz, CDCl3 /TMS, δ): 7.5(m,2H), 7.3(m,3H), 4.4(s,2H), 4.1(m,2H), 3.6(t,2H), 2.7(br t,2H), 1.8-1.1(m,16H). MSCI: 344 (MH+, base).

1. stirringthe mixture stirred for 1 hour
2. temperaturethe mixture was heated
3. temperatureto reflux for 24 hours
4. temperatureAfter cooling
5. customthe solvent was removed by distillation under reduced pressure
6. dissolutionThe residue was dissolved in ethyl acetate
7. extractionextracted with water (3×100 mL), brine (100 mL)
8. dry with materialdried (MgSO4)
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customThe crude product was purified by chromatography on silica gel
12. washeluting with 5% ethyl acetate in hexanes
13. concentrationconcentrated under reduced pressure