Iodine → 4-Iodo-3-methoxy-6-pyridin-4-yl-pyridazine

Temperature

0 °C

45 ml 1.6M solution of n-Butyllithium in hexane are added at −30° C. to a 10.2 g 2,2,6,6-tetramethylpiperidine in 100 ml THF, and the mixture is stirred at 0° C. for 30 min. After cooling to −75° C., 11.2 g 3-Methoxy-6-pyridin-4-yl-pyridazine dissolved 300 ml THF are added, and the solution is stirred at −75° C. for 35 min. The cold (−75° C.) reaction mixture is subsequently added to a cold (−75° C.) solution of 18.3 g iodine in 400 ml THF and stirred at −75° C. for 1.5 h. The reaction is quenched by adding 80 ml methanol/THF (1:1) at −75° C. and 300 ml saturated aqueous NaHCO3 at room temperature and extracted with dichloromethane. The organic layer is washed with 5% aqueous Na2S2O3 and saturated sodium chloride solution, dried (MgSO4) and the solvent removed. The crude product is purified by chromatography on silica gel to yield 14.4 g of 4-Iodo-3-methoxy-6-pyridin-4-yl-pyridazine.

1. temperatureAfter cooling to −75° C.
2. additionare added
3. stirringthe solution is stirred at −75° C. for 35 min
4. customThe cold (−75° C.) reaction mixture
5. stirringstirred at −75° C. for 1.5 h
6. customThe reaction is quenched
7. additionby adding 80 ml methanol/THF (1:1) at −75° C.
8. extraction300 ml saturated aqueous NaHCO3 at room temperature and extracted with dichloromethane
9. washThe organic layer is washed with 5% aqueous Na2S2O3 and saturated sodium chloride solution
10. dry with materialdried (MgSO4)
11. customthe solvent removed
12. customThe crude product is purified by chromatography on silica gel

ORD record

ord-b9aca316e75c48e0908d67200d07303e

Source dataset

uspto-grants-2011_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07968546B2