反应详情

To a solution of ethyl N-Boc-piperidine-4-carboxylate (10.0 g, 38.86 mmol) in THF (200 mL) was added LDA (2 M solution in Hexane, 38.86 mL, 77.72 mmol) at −78° C. and stirred for 30 min. 3-bromo propionitrile (6.25 g, 46.63 mmol) was then added at −78° C. The resulting reaction mixture was stirred at −60° C. for 4 h and quenched with saturated NH4Cl solution. Ethyl acetate was added and the organic layer was extracted with water and brine. The organic layer was dried over Na2SO4, filtered and concentrated. The crude product was purified by column chromatography using 10% ethyl acetate in hexane to yield the title compound as a pale yellow liquid (5.0 g, 40%). [1H-NMR (DMSO-d6, 300 MHz): δ 4.15 (q, 2H), 3.78-3.54 (m, 2H), 2.93-2.72 (m, 2H), 2.43 (t, 2H), 2.02-1.78 (m, 4H), 1.45-1.29 (m, 11H), 1.22 (t, 3H); HPLC RtA=4.703 min (93%); LCMS RtA=1.881, [M+H-Boc]+=211.1].

1. customThe resulting reaction mixture
2. stirringwas stirred at −60° C. for 4 h
3. customquenched with saturated NH4Cl solution
4. additionEthyl acetate was added
5. extractionthe organic layer was extracted with water and brine
6. dry with materialThe organic layer was dried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated
9. customThe crude product was purified by column chromatography