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

Temperature

0 °C

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.

1. additionwas added 26 mL (76.1 mmol
2. temperatureThe solution was then cooled to −78° C.
3. stirringthe solution stirred at −78° C. for 2 hrs
4. customThe reaction was quenched by the addition of saturated aqueous sodium thiosulfate solution
5. temperatureto warm to room temperature
6. additiondiluted with CH2Cl2 and water
7. customthe CH2Cl2 layer separated
8. extractionthe aqueous layer extracted once more with CH7Cl2
9. washthe combined CH2Cl2 layers washed with brine
10. dry with materialdried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated in vacuo
13. customThe crude product was purified by column chromatography (silica)
14. washeluting with hexane/ethyl acetate

ORD record

ord-cca4eae5a75349f68df12ad5e229fb5c

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08598174B2