反应详情

In 800 ml of tetrahydrofuran, 81.0 g (0.40 mole) of 2-bromobenzylthiol were dissolved, followed by the dropwise addition of 516 ml (0.84 mole) of n-butyl lithium (1.6 mole, a hexane solution) at −78° C. over 6 hours. After stirring at the same temperature for 1.5 hours, a solution of 79.5 g (0.40 mole) of N-tert-butoxycarbonyl-4-piperidone in 800 ml of tetrahydrofuran was added dropwise to the reaction mixture over 3 hours and then the mixture was stirred for a further 1 hour. A saturated aqueous solution of ammonium chloride was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to afford a residue. To the residue, 2 liters of 4N sulfuric acid were added and the mixture was heated under reflux for 14 hours. Under ice-cooling, the reaction mixture was made alkaline with 350 g (8.75 mole) of sodium hydroxide, followed by addition of 102 g (0.47 mole) of di-tert-butyl dicarbonate. The resulting mixture was stirred for 1 hour. The reaction mixture was extracted with methylene chloride. The organic layer was washed with a saturated aqueous solution of sodium chloride and then dried over anhydrous sodium sulfate. The residue obtained by distilling off the solvent of the extract under reduced pressure was purified by chromatography on a silica gel column (eluting solvent; n-hexane:ethyl acetate=97:3), whereby 56 g of the title compound were obtained as white crystals.

1. stirringthe mixture was stirred for a further 1 hour
2. extractionthe mixture was extracted with ethyl acetate
3. washThe organic layer was washed with a saturated aqueous solution of sodium chloride
4. dry with materialdried over anhydrous sodium sulfate
5. distillationthe solvent was distilled off under reduced pressure
6. customto afford a residue
7. temperaturethe mixture was heated
8. temperatureunder reflux for 14 hours
9. temperatureUnder ice-cooling
10. stirringThe resulting mixture was stirred for 1 hour
11. extractionThe reaction mixture was extracted with methylene chloride
12. washThe organic layer was washed with a saturated aqueous solution of sodium chloride
13. dry with materialdried over anhydrous sodium sulfate
14. customThe residue obtained
15. distillationby distilling off the solvent of the
16. extractionextract under reduced pressure
17. customwas purified by chromatography on a silica gel column (eluting solvent; n-hexane:ethyl acetate=97:3)