反应详情

温度

-78 °C

A four-neck flask equipped with a mechanical stirrer, thermowell, and addition funnel was charged with 2,2,6,6-tetramethylpiperidine (25.1 mL, 147.7 mmol) and anhydrous THF (200 mL). The solution was cooled to −10° C.-0° C. and n-BuLi (2.5 M in hexanes, 59 mL, 147.7 mmol) was added over 10 min. The solution was stirred for 15-20 min then further cooled to −78° C. A mixture of freshly purified 3,6-dichloro-pyridazine (10 g, 67.1 mmol) and trimethylsilyl chloride (9.3 mL, 73.8 mmol) in THF (100 mL) was added dropwise via an addition funnel. The dark red solution was stirred at −78° C. for 1 hr, at which point the reaction was complete. The reaction was quenched cold with saturated ammonium chloride solution (100 mL) and immediately diluted with MTBE (200 mL). The layers were separated while still cold (additional water was added if necessary until all solids dissolved) and the aqueous phase was washed with MTBE (100 mL). The combined organic solution was washed with dilute citric acid solution (30 mL portions) until the aqueous washes were pH 6-7. The organic solution was then washed with brine, dried over Na2SO4, and concentrated to a residue. The crude material was purified by column chromatography on silica gel (100 g, 2:1 heptane:EtOAc) to provide 13.6 g of 20 as a reddish oil.

1. customA four-neck flask equipped with a mechanical stirrer
2. additionthermowell, and addition funnel
3. temperatureThe solution was cooled to −10° C.-0° C.
4. additionwas added dropwise via an addition funnel
5. stirringThe dark red solution was stirred at −78° C. for 1 hr, at which
6. customThe reaction was quenched cold with saturated ammonium chloride solution (100 mL)
7. additionimmediately diluted with MTBE (200 mL)
8. customThe layers were separated while still cold (additional water
9. additionwas added if necessary until all solids
10. dissolutiondissolved) and the aqueous phase
11. washwas washed with MTBE (100 mL)
12. washThe combined organic solution was washed with dilute citric acid solution (30 mL portions) until the aqueous washes
13. washThe organic solution was then washed with brine
14. dry with materialdried over Na2SO4
15. concentrationconcentrated to a residue
16. customThe crude material was purified by column chromatography on silica gel (100 g, 2:1 heptane:EtOAc)