反应详情

温度

0 °C

To a stirred solution of diisopropylamine (1.59 ml; 11.3 mmol) in THF (10 ml) at 0° C. was added dropwise butyl lithium (2.5 M in hexanes; 4.51 ml; 11.3 mmol). The mixture was stirred at 0° C. for 15 minutes then cooled to −78° C. A solution of 4-cyclopropylmethylsulfanyl-cyclohexanecarbonitrile (2 g; 10.2 mmol) in THF (10 ml) was added dropwise. On complete addition, the mixture was stirred at −78° C. for 30 minutes. Cyclopropanecarboxaldehyde (0.91 ml; 12.2 mmol) was added dropwise and the mixture was allowed to warm slowly to room temperature and stir for 64 hours. The mixture was quenched with brine (50 ml) and extracted with EtOAc (2×75 ml). The combined organics were washed with saturated sodium hydrogen carbonate solution (50 ml) and brine (50 ml), dried (MgSO4) and evaporated in vacuo to give an orange oil. The crude product was chromatographed on silica eluted with 25-30% EtOAc in hexane to give the product as an orange oil (1.9339 g). 1H NMR (400 MHz, DMSO): δ 5.29 (1H, d, J 4.9), 2.76 (1H, dd, J 4.9, 7.8), 2.68-2.58 (1H, m), 2.15-2.11 (1H, m), 2.04-1.98 (4H, m), 1.56-1.38 (4H, m), 0.98-0.88 (2H, m), 0.52-0.48 (3H, m), 0.45-0.37 (1H, m), 0.34-0.28 (2H, m), 0.19-0.17 (2H, m). m/z=266 (M+H+).

1. temperaturethen cooled to −78° C
2. additionOn complete addition
3. stirringthe mixture was stirred at −78° C. for 30 minutes
4. temperatureto warm slowly to room temperature
5. stirringstir for 64 hours
6. customThe mixture was quenched with brine (50 ml)
7. extractionextracted with EtOAc (2×75 ml)
8. washThe combined organics were washed with saturated sodium hydrogen carbonate solution (50 ml) and brine (50 ml)
9. dry with materialdried (MgSO4)
10. customevaporated in vacuo
11. customto give an orange oil
12. customThe crude product was chromatographed on silica
13. washeluted with 25-30% EtOAc in hexane