反应详情

2-Sulfanyl-7-(methoxy)carbonyl-1,3-benzoxazole (1.00 g) [see Preparation 49] was added to thionyl chloride (4.9 ml) followed by dimethylformamide (0.37 ml) and the mixture heated at reflux for 10 minutes. The mixture was cooled and the solvent removed at reduced pressure, the residue was azeotroped twice with xylene to afford a tan solid. This solid was immediately dissolved in acetonitrile (20 ml) and N-ethyldiisopropylamine (3.3 ml) and (2S)-2-[(benzyloxy)carbonyl]piperidinium chloride (1.22 g) was added and the mixture was then heated at reflux for 7 hours. The reaction was cooled, the solvent removed at reduced pressure, and the residue dissolved in ethyl acetate and washed sequentially with 1M aqueous citric acid solution, saturated aqueous sodium hydrogen carbonate solution, brine, then dried over magnesium sulfate and the solvent removed at reduced pressure. The crude product was purified by column chromatography on silica gel eluting with a solvent gradient of 5:1, by volume, hexane: ethyl acetate to afford benzyl (2S)-1-[7-(methoxy)carbonyl-1,3-benzoxazol-2-yl]-2-piperidinecarboxylate (0.44 g) as an orange gum.

1. temperaturethe mixture heated
2. temperatureat reflux for 10 minutes
3. temperatureThe mixture was cooled
4. customthe solvent removed at reduced pressure
5. customthe residue was azeotroped twice with xylene
6. customto afford a tan solid
7. temperaturethe mixture was then heated
8. temperatureat reflux for 7 hours
9. temperatureThe reaction was cooled
10. customthe solvent removed at reduced pressure
11. dissolutionthe residue dissolved in ethyl acetate
12. washwashed sequentially with 1M aqueous citric acid solution, saturated aqueous sodium hydrogen carbonate solution, brine
13. dry with materialdried over magnesium sulfate
14. customthe solvent removed at reduced pressure
15. customThe crude product was purified by column chromatography on silica gel eluting with a solvent gradient of 5:1, by volume, hexane