反应详情

A solution of (S)-ethyl 1-(3-methylbutanoyl)piperidine-3-carboxylate (Example 5e, 37.4 g, 154.97 mmol) in anhydrous THF (200 mL) was cooled down to 0° C. and treated with LiCl (17 g, 401.04 mmol). After stirring for 5 min, NaBH4 (15 g, 396.50 mmol) was added at the same temperature. The reaction was cooled down further to −20 C and anhydrous ethanol (400 mL) was added dropwise. The reaction was kept on the cooling bath, allowed to warm up slowly to room temperature and stirred overnight. Ethanol (100 mL) was added and the reaction was treated portionwise with saturated aqueous citric acid solution (600 mL) and stirred for another 30 min. Volatiles were removed under vacuum to give a thick colorless material. Water (100 mL) and DCM (800 mL) were added to the residue and the mixture was stirred vigorously for 15 minutes. The phases were separated and the aqueous phase was further extracted with DCM (2×800 ML). The combined organic extract was washed with brine and dried over Na2SO4. The solvent was removed under vacuum to give a colorless residue that was purified by chromatography on silica gel (3eluent: Hex/EtOAc 0-100) to yield the clean product (29.65 g, 148.79 mmol, 96%).

1. additionwas added dropwise
2. stirringstirred overnight
3. stirringstirred for another 30 min
4. customVolatiles were removed under vacuum
5. customto give a thick colorless material
6. stirringthe mixture was stirred vigorously for 15 minutes
7. customThe phases were separated
8. extractionthe aqueous phase was further extracted with DCM (2×800 ML)
9. extractionThe combined organic extract
10. washwas washed with brine
11. dry with materialdried over Na2SO4
12. customThe solvent was removed under vacuum
13. customto give a colorless residue that
14. customwas purified by chromatography on silica gel (3eluent: Hex/EtOAc 0-100)