3,5-Dibromopyridine → 3-Bromo-5-(4-methoxyphenoxy)pyridine

HRID 967916

Reaction equation

HRID 967916 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=1.[CH3:9][O:10][C:11]1[CH:32]=[CH:31][C:14]([O:15]C2C=C(N3CCC4(NCCC4)C3)C=NC=2)=[CH:13][CH:12]=1.COC1C=CC([O-])=CC=1.[Na+]>CN(C)C=O>[Br:8][C:6]1[CH:5]=[N:4][CH:3]=[C:2]([O:15][C:14]2[CH:31]=[CH:32][C:11]([O:10][CH3:9])=[CH:12][CH:13]=2)[CH:7]=1

Participants

5

Reactant 3

HCID 693693,5-Dibromopyridine2×HCID 22291247HCID 22291247, compoundHCID 23679016Sodium 4-methoxyphenolate

Product 1

HCID 120162263-Bromo-5-(4-methoxyphenoxy)pyridine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In an alternative approach to the synthesis of pyridine-substituted pyridyl diazaspiroalkanes, 3,5-dibromopyridine can be converted into the corresponding 5-alkoxy-3-bromo- and 5-aryloxy-3-bromopyridines by the action of sodium alkoxides or sodium aryloxides. Procedures such as those described by Comins et al., J. Org. Chem. 55: 69 (1990) and Hertog et al., Recueil Trav. Chim. Pays-Bas 74: 1171 (1955) are used. This is exemplified by the preparation 7-(5-(4-methoxyphenoxy)-3-pyridyl)-1,7-diazaspiro[4.4]nonane. Reaction of 3,5-dibromopyridine with sodium 4-methoxyphenoxide in N,N-dimethylformamide gives 3-bromo-5-(4-methoxyphenoxy)pyridine. Coupling of 3-bromo-5-(4-methoxyphenoxy)pyridine with 1-benzyl-7-(3-pyridyl)-1,7-diazaspiro[4.4]nonane in the presence of sodium tert-butoxide, and a catalytic amount of tris(dibenzylideneacetone)dipalladium(0) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl, in toluene, followed by hydrogenolysis of the benzyl protecting group, will provide 7-(5-(4-methoxyphenoxy)-3-pyridyl)-1,7-diazaspiro[4.4]nonane.

Sources & evidence

ORD record
ord-a35fbd64f3c44b078ea183e3efcab26f
Source dataset
uspto-grants-2005_10
Patent number
US06956042B2

Linked notes

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