Pyridine N-Oxide → 3-(4-Methylphenyl)pyridine-2-carbonitrile

HRID 2297936Notes

Reaction equation

HRID 2297936 reaction equation
[N+]1([O-])C=CC=CC=1.Br[C:9]1[C:10]([C:15]#[N:16])=[N:11][CH:12]=[CH:13][CH:14]=1.C[Si](C#N)(C)C.[CH3:23][C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1>C(#N)C>[C:15]([C:10]1[C:9]([C:27]2[CH:28]=[CH:29][C:24]([CH3:23])=[CH:25][CH:26]=2)=[CH:14][CH:13]=[CH:12][N:11]=1)#[N:16]

Participants

6

Reactant 4

HCID 12753Pyridine N-OxideHCID 79799Tolylboronic acidHCID 82115Trimethylsilyl cyanideHCID 8176943-Bromopyridine-2-carbonitrile2×

Product 1

HCID 153301703-(4-Methylphenyl)pyridine-2-carbonitrile

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Synthetic Scheme XXVIII shows the 4-step preparation of the alkylating reagent 2-cyano-3-(4-bromomethylphenyl)pyridine (79) from 3-bromopyridine (80) (Aldrich). In step 1, the pyridine 80 was reacted with hydrogen peroxide in acetic acid at reflux to give the pyridine N-oxide 81. In step 2, the N-oxide 81 was converted to 3-bromo-2-cyanopyridine (82) by reaction with trimethysilylcyanide and triethyl anine in acetonitrile at reflux. In step 3, the nitrile 82 was coupled with 4-methylphenylboronic acid (56) (Scheme XXIV) using Snieckus conditions (Scheme XIII) to give 2-cyano-3-(4-methylphenyl) pyridine (83). In step 4, 83 was brominated with NBS/AIBN in carbon tetrachloride at reflux to give the desired alkylating reagent 79.

Workup

  1. temperatureat reflux

Sources & evidence

ORD record
ord-ba6432a067944a219c051352d541ee67
Source dataset
uspto-grants-2002_12
Patent number
US06492397B1

Reaction notes

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