Toluene → 6-Benzyloxy-5-hydroxynicotinonitrile

HRID 1596702Notes

Reaction equation

HRID 1596702 reaction equation
Br[C:2]1[CH:3]=[C:4]([OH:9])[C:5](=[O:8])[NH:6][CH:7]=1.[C:10]1([CH3:16])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[CH3:17][N:18](C=O)C>C(=O)([O-])[O-].[Ag+2]>[CH2:16]([O:8][C:5]1[C:4]([OH:9])=[CH:3][C:2]([C:17]#[N:18])=[CH:7][N:6]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

5

Reactant 3

HCID 1140TolueneHCID 6228DimethylformamideHCID 125630835-Bromopyridine-2,3-diol

Product 1

HCID 217026806-Benzyloxy-5-hydroxynicotinonitrile

Reagents, catalysts & solvents 1

HCID 178418647HCID 178418647, compoundCatalyst

Procedure

For example, 5-bromo3-hydroxy-2 (1H)-pyridinone is protected as the 3-t-butyloxycarbonyl derivative (by treatment with di-t-butyl dicarbonate) and treated with e.g. an appropriately substituted benzyl bromide in the presence of silver carbonate in an inert solvent such as toluene. The resulting 2-benzyloxy substituted derivative is then reacted with cuprous cyanide in an inert solvent such as DMF at elevated temperature to yield 6-benzyloxy-5-hydroxynicotinonitrile. Condensation with a Grignard reagent (e.g. methylmagnesium bromide) yields 6-benzyloxy-5-hydroxy-3-acetylpyridine which is further reacted, with e.g. ethyl bromoacetate, to give the starting material for the Horner-Emmons condensation of process (a).

Sources & evidence

ORD record
ord-62fdd4ad505b4940bbef89d66d7b04e7
Source dataset
uspto-grants-2001_09
Patent number
US06291530B1

Reaction notes

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