反应详情

温度

-78 °C

To a THF solution (0.5 M) of 2-bromopyridine (2.8 eq.) was added, at −78° C., n-butyl lithium (1.6 M hexane solution, 2.8 eq.) dropwise over 15 min. The resulting yellow suspension was stirred at −78° C. for a further 15 min before an ether solution (0.5 M) of cuprous iodide (1.4 eq.) and dibutyl sulfide (2.8 eq.) was added over 15 min. The resulting reaction mixture was allowed to stir at −78° C. for 15 min and then at 0° C. for 15 min. Finally, to this was added dropwise at 0° C., a THF solution (0.1 M) of (2E)-2-cyano-N-cyclopropyl-3-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}-N-(2,3-dimethylbenzyl)acrylamide (Example 1, Step 2, 1 eq.). The resulting emerald green suspension was stirred at 0° C. for 15 min and then at RT for 2 h. The reaction was quenched with 3:1 (v:v) sat. aq. NH4Cl:conc. aq. NH4OH solution and extracted with ether. The combined organic extracts were washed with brine, dried over MgSO4, filtered and the filtrate concentrated in vacuo. The crude product thus obtained was purified by way of column chromatography (SiO2, 10:1→1:1 (v/v) Hex:EtOAc). The title compound was isolated as a mixture of diastereomers.

1. additionwas added over 15 min
2. customThe resulting reaction mixture
3. waitat 0° C. for 15 min
4. additionFinally, to this was added dropwise at 0° C.
5. stirringThe resulting emerald green suspension was stirred at 0° C. for 15 min
6. waitat RT for 2 h
7. customThe reaction was quenched with 3:1 (v:v) sat. aq. NH4Cl
8. extractionaq. NH4OH solution and extracted with ether
9. washThe combined organic extracts were washed with brine
10. dry with materialdried over MgSO4
11. filtrationfiltered
12. concentrationthe filtrate concentrated in vacuo
13. customThe crude product thus obtained
14. customwas purified by way of column chromatography (SiO2, 10:1→1:1 (v/v) Hex:EtOAc)