反应详情

温度

120 °C

tert-Butyl (R)-1-(4-bromophenyl)-4-((R)-3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-4-oxobutan-2-ylcarbamate (6A) (as prepared in Example 6, Step A) (0.114 mmol, 0.070 g) and 4-(methoxycarbonyl)phenylboronic acid (0.148 mmol, 0.027 g) were added to a 5 mL microwave vessel equipped with a magnetic stir bar. Dioxane (2 mL) and Na2CO3 (1 mL of a 2 M aq. soln.) were then added and the reaction vessel was flushed with nitrogen gas. PdCl2(dppf) (0.006 mmol, 0.004 g) was added, the reaction vessel was sealed and placed in a microwave reactor and heated to 120° C. for 15 minutes. The reaction solution was then poured into water, extracted with ethyl acetate, and washed once with saturated aqueous sodium chloride. The organic layer was collected and subsequently dried with anhydrous Na2SO4 and filtered. This filtrate was collected, concentrated, and dried in-vacuo. This crude material was directly purified by preparative LC/MS (25-85% CH3CN in H2O). The resultant fractions were collected and the solvent was removed in-vacuo affording methyl 4′-((R)-2-(tert-butoxycarbonylamino)-4-((R)-3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-4-oxobutyl)biphenyl-4-carboxylate (53A) as a clear oil. (0.08 mmol, 0.054 g, 70% yield). ESI-MS: m/z 669.4 (M+H)+.

1. customequipped with a magnetic stir bar
2. addition) were then added
3. customthe reaction vessel was flushed with nitrogen gas
4. customthe reaction vessel was sealed
5. customplaced in a microwave reactor
6. extractionextracted with ethyl acetate
7. washwashed once with saturated aqueous sodium chloride
8. customThe organic layer was collected
9. dry with materialsubsequently dried with anhydrous Na2SO4
10. filtrationfiltered
11. customThis filtrate was collected
12. concentrationconcentrated
13. customdried in-vacuo
14. customThis crude material was directly purified by preparative LC/MS (25-85% CH3CN in H2O)
15. customThe resultant fractions were collected
16. customthe solvent was removed in-vacuo