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

HRID 1450484Notes

Reaction equation

HRID 1450484 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(N(CC)CC)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

7

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 2

HCID 6342AcetonitrileSolventHCID 8471TriethylamineSolvent

Procedure

Synthetic Scheme XXVIII shows the 4-step preparation of the alkylating reagent 2-cyano-3-(4-bromomethylphenyl)pyridine (75) from 3-bromopyridine (76) (Aldrich). In step 1, the pyridine 76 was reacted with hydrogen peroxide in acetic acid at reflux to give the pyridine N-oxide 77. In step 2, the N-oxide 77 was converted to 3-bromo-2-cyanopyridine (78) by reaction with trimethysilylcyanide and triethylamine in acetonitrile at reflux. In step 3, the nitrile 78 was coupled with 4-methylphenylboronic acid (52) (Scheme XXIV) using Snieckus conditions (Scheme XIII) to give 2-cyano-3-(4-methylphenyl)pyridine (79). In step 4, 79 was brominated with NBS/AIBN in carbon tetrachloride at reflux to give the desired alkylating reagent 75. ##STR82##

Workup

  1. temperatureat reflux

Sources & evidence

ORD record
ord-481333ef1b3242dd902b42a734c31283
Source dataset
uspto-grants-1997_02
Patent number
US05602153

Reaction notes

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