反应详情

温度

-40 °C

(1R,6S)-3-benzyl 7-tert-butyl 3,7-diazabicyclo[4.1.0]heptane-3,7-dicarboxylate (220 mg, 0.663 mmol), CuI (25 mg, 0.2 equiv), and a stirring bar were put in a 100-mL flask. The flask was evacuated and backfilled with N2 gas (3×). Dry THF (5 mL) was added and the mixture was cooled to −40° C. 1 M Cyclohexylmagnesium bromide in THF (2.0 mL, 3 equiv) was added slowly. After 8 min, the reaction mixture was allowed warmed slowly to rt. After 20 min, the reaction mixture turned into black. After stirring a further 2 h, LC-MS showed the reaction was complete. Satd aq NH4Cl solution (5 mL) was added to quench the reaction. The reaction mixture was partitioned between EtOAc (50 mL) and satd aq NH4Cl solution (20 mL). The aqueous layer was extracted with EtOAc (20 mL). The combined EtOAc layers were washed with water (15 mL) and brine (15 mL), and dried over Na2SO4. After concentration, the residue was purified by preparative HPLC to afford (3S,4S)-benzyl 3-(tert-butoxycarbonylamino)-4-cyclohexylpiperidine-1-carboxylate (62.3 mg, 23% yield) and (3S,4S)-benzyl 4-(tert-butoxycarbonylamino)-3-cyclohexylpiperidine-1-carboxylate (15 mg). LC-MS (3 min) tR=2.33 min., m/z 439 (M+Na).

1. customThe flask was evacuated
2. additionDry THF (5 mL) was added
3. temperaturethe reaction mixture was allowed warmed slowly to rt
4. waitAfter 20 min
5. customto quench
6. customthe reaction
7. customThe reaction mixture was partitioned between EtOAc (50 mL)
8. extractionThe aqueous layer was extracted with EtOAc (20 mL)
9. washThe combined EtOAc layers were washed with water (15 mL) and brine (15 mL)
10. dry with materialdried over Na2SO4
11. concentrationAfter concentration
12. customthe residue was purified by preparative HPLC