反应详情

温度

3 °C

A solution of THF (2.5 mL) and toluene (10 mL), and methylmagnesium chloride (3.0 M, 9.7 mL) were stirred at −20° C. under N2 atmosphere followed by the addition of t-BuOH (0.5 mL, 5.79 mmol) in THF (7 mL) dropwise. The solution was allowed to stir for 30 min and warmed to 3° C. and cooled backed down to −20° C. followed by the addition of the methyl 6-chloropyridazine-3-carboxylate (1.0 g, 5.79 mmol) in portions. The solution quickly turned dark violet and was stirred at 0° C. for 30 min. The solution was then poured into a flask containing 1 N aqueous hydrochloric acid at −5° C., diluted with ethyl acetate, and stirred for 10 min. The layers were then separated and the organic layer was washed with saturated aqueous sodium bicarbonate and brine. The acidic aqueous layer was neutralized with saturated aqueous sodium bicarbonate and extracted with ethyl acetate. The organic layers were combined and concentrated in vacuo. Purification via flash chromatography (silica, 0-100% ethyl acetate/hexanes) provided the title compound. LRMS (ESI) calcd for C7H10ClN2O [M+H]+: 173.1, Found: 173.1

1. temperaturecooled
2. custombacked down to −20° C.
3. stirringThe solution quickly turned dark violet and was stirred at 0° C. for 30 min
4. additionThe solution was then poured into a flask
5. stirringstirred for 10 min
6. customThe layers were then separated
7. washthe organic layer was washed with saturated aqueous sodium bicarbonate and brine
8. extractionextracted with ethyl acetate
9. concentrationconcentrated in vacuo
10. customPurification via flash chromatography (silica, 0-100% ethyl acetate/hexanes)