反应详情

温度

0 °C

Under nitrogen, a solution of bis-(2-chloro-ethyl)-carbamic acid tert-butyl ester* (1.54 g, 6.36 mmol) in toluene (10 mL) was cooled in ice. 4-(4-Chloro-benzyl)-pyridine (1.30 g, 6.36 mmol) was added, followed over two minutes by sodium hexamethyldisilazide solution (10 mL, 20 mmol, 2M in THF). The mixture was stirred at 0° C. for 3.5 hours then allowed to warm to room temperature and stirred for a further 20 hours. Methanol was added then the mixture was concentrated in vacuo. The residue was taken up in ethyl acetate and washed with 1N hydrochloric acid (×3) and brine, dried (MgSO4), filtered and concentrated to afford a residue which was purified by column chromatography (SiO2), eluting with gradient of 2M methanolic ammonia in dichloromethane (1% to 5%). A second purification by column chromatography (SiO2), eluting with 50% ethyl acetate/petrol gave the title compound (16 mg, 0.7%). LCMS (PS-A2) Rt 2.65 min [M+H]+ 373. * This starting material can be made by the method described in J. Chem. Soc., Perkin Trans 1, 2000, p 3444-3450

1. temperatureto warm to room temperature
2. stirringstirred for a further 20 hours
3. concentrationthe mixture was concentrated in vacuo
4. washwashed with 1N hydrochloric acid (×3) and brine
5. dry with materialdried (MgSO4)
6. filtrationfiltered
7. concentrationconcentrated
8. customto afford a residue which
9. customwas purified by column chromatography (SiO2)
10. washeluting with gradient of 2M methanolic ammonia in dichloromethane (1% to 5%)
11. customA second purification by column chromatography (SiO2)
12. washeluting with 50% ethyl acetate/petrol