反应详情

温度

-65 °C

A three-necked, 1000 mL round bottom flask equipped with a magnetic stir bar and a gas inlet tubing was charged with N-FMOC-N-allyldecylamine (˜0.099 mol) in dichloromethane (280 mL) and methanol (50 mL). The mixture was cooled in a −65° C. dry ice-chloroform bath and purged with a stream of dilute ozone in oxygen for 2.5 hours (internal temperature about −55° C.; flow rate for dilute ozone in oxygen about 1.0 L/min). The reaction was monitored by HPLC (retention time for starting material=7.96 min; retention time for product=5.82 min). Upon disappearance of the allyl starting material, ozone purging was discontinued and the mixture was purged with nitrogen for 20 minutes to remove excess ozone. The reaction mixture was then treated with triethylamine (24.8 mL, 0.178 mol) at −55° C., warmed to 21° C., and stirred for 3 hours. The reaction mixture was washed with water (50 mL); 0.01 N HCl (50 mL) and the organic layer was concentrated in vacuo to give an oil. Heptane (150 mL) was added and the mixture was concentrated in vacuo to azeotropically remove water and dichloromethane. This azeotropic procedure was repeated two more times using heptane (150 mL) to give a final volume of about 100 mL. The resulting organic solution was charged to a 200 mL three-necked round bottom flask and cooled to 15° C. in a water bath. Pieces of ice were added slowly to the water bath to cool the mixture to 5° C. in a period of 40 minutes (the mixture was seeded at approximately 10° C.). The cloudy mixture was further cooled to −10° C. and stirred for 2.5 hours. The resulting suspension was filtered through a Buchner funnel and the precipitate was washed with ice cold heptane (20 mL×2). The precipitate was collected and dried in vacuo (25 mmHg) for 6 hours to give N-FMOC-2-(n-decylamino)acetaldehyde (25.6 g; 61% yield; 99% purity) as a white waxy powder.

1. customA three-necked, 1000 mL round bottom flask equipped with a magnetic stir bar and a gas inlet tubing
2. custompurged with a stream of dilute ozone in oxygen for 2.5 hours (internal temperature about −55° C.; flow rate for dilute ozone in oxygen about 1.0 L/min)
3. customwas monitored by HPLC (retention time for starting material=7.96 min; retention time for product=5.82 min)
4. customthe mixture was purged with nitrogen for 20 minutes
5. customto remove excess ozone
6. temperaturewarmed to 21° C.
7. washThe reaction mixture was washed with water (50 mL)
8. concentration0.01 N HCl (50 mL) and the organic layer was concentrated in vacuo
9. customto give an oil
10. concentrationthe mixture was concentrated in vacuo to azeotropically remove water and dichloromethane
11. customto give a final volume of about 100 mL
12. additionThe resulting organic solution was charged to a 200 mL three-necked round bottom flask
13. temperaturecooled to 15° C. in a water bath
14. temperatureto cool the mixture to 5° C. in a period of 40 minutes (the mixture
15. customwas seeded at approximately 10° C.
16. temperatureThe cloudy mixture was further cooled to −10° C.
17. stirringstirred for 2.5 hours
18. filtrationThe resulting suspension was filtered through a Buchner funnel
19. washthe precipitate was washed with ice cold heptane (20 mL×2)
20. customThe precipitate was collected
21. customdried in vacuo (25 mmHg) for 6 hours