反应详情

温度

23 °C

A 50 mL three-necked round bottom flask equipped with an addition funnel, magnetic stirrer, heating mantel, and thermocouple was charged under nitrogen dry DMAc (2 mL), I2 (38.1 mg, 0.15 mol) and zinc powder activated (washed with 10% HCl, rinsed with H2O and acetone) (393 mg, 6 mol). The resulting mixture was stirred at 23° C. until the red color of I2 disappeared (2 minutes). A solution of Boc-β-iodo-L-alanine methyl ester (1 g, 3 mol) in DMAc (2 mL) was added slowly, (temperature change from 21° C. to 29° C.) and the resulting mixture was stirred at 80° C. for 0.5-1 hour, then co cooled to 35° C. To the resulting mixture were added, successively, 4-bromo-3,5-dimethyl-benzonitrile (315 mg, 1.5 mol) in DMAc (6 mL), P(o-tol)3 (36.5 mg, 0.12 mol) and Pd2(dba)3 (55 mg, 0.06 mol). The resulting mixture was heated to 70° C., with stirring for 1 hour, then cooled to ambient temperature. The resulting mixture was diluted with EtOAc (15 mL) and filtered with STAND SUPER-CEL 815520. The EtOAc solution was quenched with 1 N HCl (40 mL) and extracted with ethyl acetate (20 mL). The combined organic phases were washed with H2O (2×50 mL) and then with 50% brine, dried over Na2SO4, filtered and evaporated to dryness in vacuo to yield a brown solid. The title compound was crystallized from EtOAc (5 mL) and heptanes (40 mL) to yield a white solid.

1. customA 50 mL three-necked round bottom flask equipped with an addition funnel, magnetic stirrer
2. temperatureheating mantel
3. additionthermocouple was charged under nitrogen dry DMAc (2 mL)
4. wash(washed with 10% HCl, rinsed with H2O and acetone) (393 mg, 6 mol)
5. custom(2 minutes)
6. stirring(temperature change from 21° C. to 29° C.) and the resulting mixture was stirred at 80° C. for 0.5-1 hour
7. temperatureco cooled to 35° C
8. additionTo the resulting mixture were added
9. temperatureThe resulting mixture was heated to 70° C.
10. stirringwith stirring for 1 hour
11. temperaturecooled to ambient temperature
12. filtrationfiltered with STAND SUPER-CEL 815520
13. customThe EtOAc solution was quenched with 1 N HCl (40 mL)
14. extractionextracted with ethyl acetate (20 mL)
15. washThe combined organic phases were washed with H2O (2×50 mL)
16. dry with materialwith 50% brine, dried over Na2SO4
17. filtrationfiltered
18. customevaporated to dryness in vacuo
19. customto yield a brown solid
20. customThe title compound was crystallized from EtOAc (5 mL) and heptanes (40 mL)
21. customto yield a white solid