Iodine → 4-Iodo-2-methoxypyridine-3-carbonitrile
Reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([O:8][CH3:9])[C:3]=1[C:10]#[N:11].BrBr.BrC1C=CN=C(OC)C=1C#N.[I:25]I>>[I:25][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([O:8][CH3:9])[C:3]=1[C:10]#[N:11]Participants
Procedure
Thus, 2-chloro-3-cyanopyridine (A18) provided 2-methoxy-3-cyanopyridine (A19) upon treatment with sodium methoxide in methanol. Lithiation of the 2-methoxy-3-cyanopyridine (A19) with LDA gave the intermediate carbanion derivative 4-lithio-2-methoxy-3-cyanopyridine (A21), which upon treatment with hexachloroethane provided the 4-chloro-2-methoxy-3-cyanopyridine (A20). Analogously, reaction with bromine provides the 4-bromo-2-methoxy-3-cyanopyridine (A22) and reaction with iodine provides the 4-iodo-2-methoxy-3-cyanopyridine (A23). All 4-halo-2-methoxy-3-cyanopyridines are highly valuable intermediates, especially for the synthesis of kinase inhibitors. Reduction of the 4-halo-2-methoxy-3-cyanopyridines, for example with DIBAL (diisobutylaluminum hydride) in solvents such as toluene, dichloromethane, or tetrahydrofuran at temperatures ranging from −80° C. to about 80° C., preferably at 20° C. provides after standard workup the 4-halo-2-methoxypyridine-3-carboxaldehydes. The 4-halo-2-methoxypyridine-3-carboxaldehydes are highly valuable synthetic intermediates. 4-chloro-2-methoxy-3-pyridinecarboxaldehyde (A9) was prepared in this manner.
Workup
- customprovides
Sources & evidence
- ORD record
- ord-39a3c8bf2bb04197b024e7d6c4edc6a5
- Source dataset
- uspto-grants-2016_03
- Patent number
- US09290503B2
Reaction notes
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