Iodine → 6-Chloro-4-iodo-3-methoxypyridazine

Participants

Reaction Conditions

Reaction Steps

In a flask containing THF (350 mL) at −30° C. under nitrogen was added 26 mL (76.1 mmol. 2.93M n-BuLi in hexanes. 2,2,6,6-tetramethylpiperidine (12.9 mL, 76.1 mmol) was then added dropwise and the resulting solution was allowed to warm to 0° C. over 50 min. The solution was then cooled to −78° C. and there was added dropwise 3-chloro-6-methoxypyridazine (1) (5.0 g, 34.6 mmol) in 50 mL THF and the resulting solution stirred at −78° C. for 30 min. Iodine (9.3 g) was then added in three portions and the solution stirred at −78° C. for 2 hrs. The reaction was quenched by the addition of saturated aqueous sodium thiosulfate solution and allowed to warm to room temperature, then diluted with CH2Cl2 and water, the CH2Cl2 layer separated, the aqueous layer extracted once more with CH7Cl2, and the combined CH2Cl2 layers washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by column chromatography (silica) eluting with hexane/ethyl acetate to give desired product 2, 5.6 g (60%), ˜95% desired regioisomer.

Provenance & Evidence