反应详情

温度

-78 °C

To a solution of 3-chloro-6-(2,6-difluorobenzyl)pyridazine (5.7 g, 23.7 mmol) in THF (300 mL) was added LHMDS (71.2 mL, 71.2 mmol, 1M solution in THF) via cannula at −78° C. After stirring for 0.5 hr at −78° C., ethyl 3-(trimethylsilyl)propynoate (6.66 mL, 35.5 mmol) was added. The reaction was allowed to warm from −78° C. to −10° C. over 3 hours. The reaction was known to be complete by LCMS analysis; and then quenched with aqueous NH4Cl, extracted with ethyl acetate. The organic layers were combined, washed with 0.5 N HCl, water, brine, dried over MgSO4, and condensed in vacuo to yield an oil. The crude material was purified via silica gel chromatography (EtOAc/Hex) to yield the title compound (9.6 g).

1. temperatureto warm from −78° C. to −10° C. over 3 hours
2. customand then quenched with aqueous NH4Cl
3. extractionextracted with ethyl acetate
4. washwashed with 0.5 N HCl, water, brine
5. dry with materialdried over MgSO4, and condensed in vacuo
6. customto yield an oil
7. customThe crude material was purified via silica gel chromatography (EtOAc/Hex)