Dimethylformamide → Methyl 3-chloro-2-cyano-pyridine-4-carboxylate

HRID 2067006Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][N:7]=[C:6](Cl)[C:5]=1[Cl:11].[CH3:13][N:14](C=O)C>[C-]#N.[Zn+2].[C-]#N.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>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][N:7]=[C:6]([C:13]#[N:14])[C:5]=1[Cl:11]

Participants

Conditions

Temperature: 190 °C

Procedure

A microwave vial was charged with 2,3-dichloro-isonicotinic acid methyl ester (7.6 g, 36.9 mmol), zinc cyanide (4.75 g, 40.6 mmol), tetrakis(triphenylphosphine)palladium (1.0 g, 0.9 mmol) and DMF (37 mL), then capped, evacuated and backfilled with nitrogen. The reaction solution was subjected to microwave irradiation, heating at 190° C. for 20 minutes, then filtered through a pad of Celite® which was washed further with ethyl acetate. The resulting mixture was washed with water, followed by a saturated solution of sodium hydrogen carbonate, then brine, dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to column chromatography (Si-PPC, gradient 0% to 100%, ethyl acetate in cyclohexane) to give the title compound as a white solid (3.1 g, 43%). 1H NMR (CDCl3, 400 MHz) 8.70 (d, J=5.0 Hz, 1H), 7.87 (d, J=5.0 Hz, 1H), 4.01 (s, 3H).

Workup

customcapped
customevacuated
customirradiation
filtrationfiltered through a pad of Celite® which
washwas washed further with ethyl acetate
washThe resulting mixture was washed with water
dry with materialbrine, dried (Na2SO4)
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-08cb7549550c42898d0b290ab6805edb
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08293763B2

Reaction notes

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