Hydrochloric Acid → 2-Methylpyridine-4-carbonitrile

HRID 1497272Notes

Reaction equation

HRID 1497272 reaction equation
Cl[C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][N:9]=1)[C:5]#[N:6].[CH3:10][Al](C)C.Cl>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:10][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][N:9]=1)[C:5]#[N:6]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 5686382-Chloro-4-cyanopyridineHCID 16682925Trimethylaluminum

Product 1

HCID 119590732-Methylpyridine-4-carbonitrileYield 57.6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A solution of 2-chloroisonicotinonitrile (2 g, 14.4 mmol), trimethylaluminum (7.94 ml, 15.9 mmol) and tetrakis(triphenylphosphine)palladium (0) (367 mg, 318 μmol) in dioxane (20.0 ml) was heated to reflux for 4 h. The reaction mixture was poured on 1N HCl and extracted two times with EtOAc. The aqueous layer was basified with 3N NaOH and extracted with EtOAc. The combined organic extracts were dried with Na2SO4 and evaporated. The remaining solid was purified by column chromatography (silica gel, dichloromethane/EtOAc 95:5) to afford the title compound (980 mg, 57%) as white solid. 1H NMR (CDCl3, 300 MHz): 2.64 (s, 3H), 7.34 (d, J=5.05 Hz 1H), 7.40 (s, 1H), 8.68 (d, J=5.05 Hz, 1H).

Workup

  1. temperatureto reflux for 4 h
  2. extractionextracted two times with EtOAc
  3. extractionextracted with EtOAc
  4. dry with materialThe combined organic extracts were dried with Na2SO4
  5. customevaporated
  6. customThe remaining solid was purified by column chromatography (silica gel, dichloromethane/EtOAc 95:5)

Sources & evidence

ORD record
ord-9e76c94f427b412781233da037c20c9b
Source dataset
uspto-grants-2015_12
Patent number
US09199938B2

Reaction notes

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