反应详情

To 20 mL of a tetrahydrofuran solution containing 1.2 mL of diisopropylamine, 5.8 mL of 1.6 mol/L butyllithium/hexane was added dropwise at −78° C., and the mixture was stirred at the same temperature for 1 hour. Thereto was added dropwise 2 mL of a tetrahydrofuran solution containing 2.0 g of 1-tert-butyl 4-ethyl piperidine-1,4-dicarboxylate, and the mixture was stirred for 1 hour. Thereto was added 1.7 mL of benzyl 3-bromopropyl ether, and the temperature of the reaction mixture was increased to room temperature, and the reaction mixture was stirred for 10 hours. Water was added thereto, and the reaction mixture was adjusted to pH 2.0 with 6 mol/L hydrochloric acid. The organic layer was separated, and the aqueous layer was extracted twice with ethyl acetate. The organic layer and the extract were combined, the resultant solution was washed with an aqueous saturated sodium chloride solution and dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue thus obtained was purified by silica gel column chromatography [eluent; hexane:ethyl acetate=10:1 ] to obtain 2.0 g of a colorless oily substance, 1-tert-butyl 4-ethyl 4-(3-(benzyloxy)propyl)piperidine-1,4-dicarboxylate.

1. additionwas added dropwise at −78° C.
2. stirringthe mixture was stirred for 1 hour
3. stirringthe reaction mixture was stirred for 10 hours
4. customThe organic layer was separated
5. extractionthe aqueous layer was extracted twice with ethyl acetate
6. washthe resultant solution was washed with an aqueous saturated sodium chloride solution
7. dry with materialdried over anhydrous magnesium sulfate
8. customthe solvent was removed under reduced pressure
9. customThe residue thus obtained
10. customwas purified by silica gel column chromatography [eluent; hexane:ethyl acetate=10:1 ]