反应详情

温度

-78 °C

The bromo (4-methylpyridin-2-yl)magnesium (10.4 mL, 2.6 mmole) was diluted by 5 mL THF and the solution was cooled to −78° C. ZnCl2 (340 mg, 2.5 mmole) was added to above solution and the mixture was slowly warmed to r.t and heated to 50 OC for 3 hrs. The mixture was cooled to −78° C. again and ethyl 7-(bromomethyl)-6-chloro-2-(trifluoromethyl)-2H-chromene-3-carboxylate from Example 16, Step 3 (1.0 g, 2.5 mmol) was added to above mixture and followed by PdCl2(PPh3)2 (18 mg, 0.025 mmole). The mixture was warmed to 50° C. for 3 hrs. LCMS indicated that around 40% product was formed. The reaction was quenched with 1 N HCl and extracted with EtOAc. The organic layer was washed with brine and dried over MgSO4. The filtrate was concentrated to afford the crude product, which was purified by RPHPLC eluted with 10 to 95% ACN in water with 0.05% TFA to give 50 mg the desired product as a brown oil (yield 5%), which had suitable purity to use without further purification.

1. temperaturethe mixture was slowly warmed
2. temperatureheated to 50 OC for 3 hrs
3. temperatureThe mixture was cooled to −78° C. again
4. temperatureThe mixture was warmed to 50° C. for 3 hrs
5. customwas formed
6. customThe reaction was quenched with 1 N HCl
7. extractionextracted with EtOAc
8. washThe organic layer was washed with brine
9. dry with materialdried over MgSO4
10. concentrationThe filtrate was concentrated
11. customto afford the crude product, which
12. customwas purified by RPHPLC
13. washeluted with 10 to 95% ACN in water with 0.05% TFA