反应详情

温度

30 °C

A 250 mL, jacketed, three necked flask equipped with an overhead stirrer, 50 mL pressure equalizing addition funnel and a temperature probe was charged with 2a (10 g, 51.7 mmol), THF (50 mL) and CuI (98 mg, 1.0 mol %) and the stirred mixture was heated to 30° C. The pressure equalizing addition funnel was charged with PhMgCl (2M in THF, 32.36 mL) and the solution was added over 20 minutes while maintaining an internal temperature of 30-32° C. After the addition was complete, the reaction mixture was heated to 45-50° C. for an additional 30 minutes and then cooled to ambient temperature. The reaction was quenched by slow addition to a cooled mixture of saturated aqueous ammonium chloride solution and water (50/50 v/v, 100 mL) while maintaining an internal temperature below 20° C. The flask was rinsed with methyl t-butyl ether (100 mL) and the rinse was transferred to the quenched reaction mixture. The biphasic mixture was stirred for 5 minutes, allowed to separate for 20 minutes and then the aqueous phase was removed. The organic phase washed with saturated sodium chloride solution (50 mL) and the organic phase was dried over sodium sulfate. The solution (a 97:7 mixture of 6a: 8a by GC analysis) was filtered and concentrated under reduced pressure until the product began to crystallize. Heptane (40 mL) was added to the slurry and the mixture was heated until a solution was obtained. The stirred solution allowed to cool to room temperature and stirred for 18 hours. The solid was collected by filtration and dried under reduced pressure at 30° C. for 18 hours affording diethyl (1-phenylpropan-2-yl)phosphoramidate (6a) as a white crystalline solid (9.12 g, 65% yield; 99.72% GC purity with 0.04% 8a present). Mp 66-67° C. (lit1 57-58° C.). 1H NMR (300 MHz, CDCl3) δ 7.36-7.08 (m, 5H), 4.14-3.85 (m, 3H), 3.85-3.66 (m, 1H), 3.58-3.32 (m, 1H), 2.81-2.61 (m, 2H), 2.38 (t, J=9.8 Hz, 1H), 1.38-1.18 (m, 6H), 1.15 (d, J=6.4 Hz, 3H).

1. customthree necked flask equipped with an overhead stirrer
2. additionaddition funnel
3. additionaddition funnel
4. additionthe solution was added over 20 minutes
5. temperaturewhile maintaining an internal temperature of 30-32° C
6. additionAfter the addition
7. temperaturethe reaction mixture was heated to 45-50° C. for an additional 30 minutes
8. temperaturecooled to ambient temperature
9. customThe reaction was quenched by slow addition to a cooled mixture of saturated aqueous ammonium chloride solution and water (50/50 v/v, 100 mL)
10. temperaturewhile maintaining an internal temperature below 20° C
11. washThe flask was rinsed with methyl t-butyl ether (100 mL)
12. customthe rinse was transferred to the quenched reaction mixture
13. customto separate for 20 minutes
14. customthe aqueous phase was removed
15. washThe organic phase washed with saturated sodium chloride solution (50 mL)
16. dry with materialthe organic phase was dried over sodium sulfate
17. additionThe solution (a 97:7 mixture of 6a
18. filtration8a by GC analysis) was filtered
19. concentrationconcentrated under reduced pressure until the product
20. customto crystallize
21. additionHeptane (40 mL) was added to the slurry
22. temperaturethe mixture was heated until a solution
23. customwas obtained
24. temperatureto cool to room temperature
25. stirringstirred for 18 hours
26. filtrationThe solid was collected by filtration
27. customdried under reduced pressure at 30° C. for 18 hours