反应详情

A solution of 1-(4-bromophenyl)cyclopropanecarboxylic acid (1000.0 mg, 0.0041480 mol) in tetrahydrofuran (30 mL, 0.4 mol) was cooled below −20° C. under a N2 atmosphere and dibutylmagnesium in heptane (1.0 M, 2.2 mL) was slowly added to the solution while the reaction temperature was maintained below −20° C. Then 2.5 M of n-butyllithium in hexane (1.8 mL) was slowly added to the mixture below −20° C. under effective stirring. After stirring below −20° C. for 1 h, a solution of tert-butyl 4-oxo-1-piperidinecarboxylate (0.909 g, 0.00456 mol) in THF (20.0 mL) was added to the mixture below −20° C. After stirring below −20° C. for 1 h, the reaction was quenched with ammonium chloride. The product was extracted with EtOAc and the combined extract was washed with brine, dried over Na2SO4, and filtered. The filtrate was concentrated and then purified by Combiflash, eluting with 5% methanol in methylene chloride.

1. temperaturewas maintained below −20° C
2. stirringAfter stirring below −20° C. for 1 h
3. customthe reaction was quenched with ammonium chloride
4. extractionThe product was extracted with EtOAc
5. extractionthe combined extract
6. washwas washed with brine
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationThe filtrate was concentrated
10. custompurified by Combiflash
11. washeluting with 5% methanol in methylene chloride