反应详情

温度

-68 °C

Equip a 250-mL round bottom flask with a magnetic a stirrer, a thermocouple, a dry ice/acetone bath, a N2 atmosphere, and an addition funnel. Charge with 2,2-dimethyl-N-pyridin-3-yl-propionamide (3.0 g, 16.8 mmol), diethylether (67 mL), and tetramethylene diamine (4.68 g, 6.08 mL, 40.3 mmol). Cool the reaction to −78° C. Add slowly via glass syringe n-butyllithium (2.5 M solution in hexane, 16.2 mL, 40.3 mmol) over 10 min. Warm the reaction to −13° C. over 2 h. Cool the reaction to −78° C. Prepare an iodine solution (I2 8.5 g, 33.6 mmol in THF (20 mL)). Add the iodine solution to the reaction via the addition funnel and stir 2.5 h. at −68° C. Quench the reaction with the addition of a saturated NH4Cl solution (40 mL) and transfer into a separatory funnel. Add ethyl acetate (100 mL). Extract and discard the lower aqueous phase. Wash the organic layer with a saturated sodium thiosulfate solution (100 mL) and extract. Wash the organic phase with saturated aqueous sodium chloride and extract. Dry the organic phase over Na2SO4 and filter. Concentrate the product via rotary evaporation. Chromatograph on silica (80 g) eluting with gradient of 100% DCM to 70% ethyl acetate/30% DCM to afford 1.19 g (23%) of the title compound. MS (ES) m/z 306 [M+1]+.

1. customEquip a 250-mL round bottom flask with a magnetic a stirrer
2. temperatureCool
3. customthe reaction to −78° C
4. temperatureWarm
5. customthe reaction to −13° C. over 2 h
6. temperatureCool
7. customthe reaction to −78° C
8. customto the reaction via the addition funnel
9. customQuench
10. customthe reaction
11. customtransfer into a separatory funnel
12. extractionExtract
13. washWash the organic layer with a saturated sodium thiosulfate solution (100 mL)
14. extractionextract
15. washWash the organic phase with saturated aqueous sodium chloride
16. extractionextract
17. dry with materialDry the organic phase over Na2SO4
18. filtrationfilter
19. concentrationConcentrate the product
20. customvia rotary evaporation
21. washChromatograph on silica (80 g) eluting with gradient of 100% DCM to 70% ethyl acetate/30% DCM