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

HRID 2234061Notes

Reaction equation

C([Li])CCC.[CH3:6][O:7][C:8]1[N:9]=[N:10][C:11]([C:14]2[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=2)=[CH:12][CH:13]=1.[I:20]I>CCCCCC.O1CCCC1>[I:20][C:13]1[CH:12]=[C:11]([C:14]2[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=2)[N:10]=[N:9][C:8]=1[O:7][CH3:6]

Participants

Conditions

Temperature: 0 °C

Procedure

45 ml 1.6M solution of n-butyllithium in hexane are added at −30° C. to a 10.2 g 2,2,6,6-tertamethylpiperidine in 100 ml THF and the mixture 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 stirred at −75° C. for 35 min. The cold (−75° C.) reaction mixture is subsequently added at a cold (−75° C.) solution of 18.3 g iodine in 400 ml THF (tetrahydrofuran) 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 ished with 5% aqueous Na2S2O3 and saturated sodium chloride solution, dried (MgSO4) and the solvens 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.

Workup

temperatureAfter cooling to −75° C
additionare added
stirringthe solution stirred at −75° C. for 35 min
customThe cold (−75° C.) reaction mixture
stirringstirred at −75° C. for 1.5 h
customThe reaction is quenched
additionby adding 80 ml methanol/THF (1:1) at −75° C.
extraction300 ml saturated aqueous NaHCO3 at room temperature and extracted with dichloromethane
dry with materialdried (MgSO4)
customthe solvens removed
customThe crude product is purified by chromatography on silica gel

Sources & evidence

ORD record: ord-526a67911aff41df843b8071f75acaa3
Source dataset: uspto-grants-2010_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07709466B2

Reaction notes

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