Dimethylcarbamoyl Chloride → Methyl 2-cyanopyridine-4-carboxylate

HRID 1397282

Reaction equation

HRID 1397282 reaction equation
C[Si]([C:5]#[N:6])(C)C.[CH3:7]N(C)C(Cl)=O.C[C:14]1[CH:22]=[N+:21]([O-])[CH:20]=[CH:19][C:15]=1[C:16]([O-:18])=[O:17]>C(Cl)Cl>[C:5]([C:20]1[CH:19]=[C:15]([CH:14]=[CH:22][N:21]=1)[C:16]([O:18][CH3:7])=[O:17])#[N:6]

Participants

5

Reactant 3

HCID 6598Dimethylcarbamoyl ChlorideHCID 82115Trimethylsilyl cyanideHCID 53443469Methylisonicotinate N-oxide

Product 1

HCID 12132796Methyl 2-cyanopyridine-4-carboxylateYield 33.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trimethylsilyl cyanide (3.8 g, 0.0386 mol) and dimethylcarbamyl chloride (5.0 g, 0.0483 mol) were added to a solution of methylisonicotinate N-oxide (5.0 g, 0.0322 mol) in dry CH2Cl2 (50 mL) at room temperature. The reaction mixture was stirred at room temperature for 12 h and then quenched with 10% K2CO3 solution. The organic product was extracted with CH2Cl2 and the organic layer was washed with H2O and brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by flash column chromatography (silica 230-400 mesh, eluent 1-2% MeOH in CH2Cl2) to afford methyl 2-cyanoisonicotinate (1.75 g, yield 33%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.97-8.95 (d, J=5.0 Hz, 1H), 8.41 (m, 1H), 8.15-8.13 (dd, J=4.8 Hz, 1.6 Hz, 1H), 3.92 (s, 3H).

Workup

  1. customquenched with 10% K2CO3 solution
  2. extractionThe organic product was extracted with CH2Cl2
  3. washthe organic layer was washed with H2O and brine
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by flash column chromatography (silica 230-400 mesh, eluent 1-2% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-3f60376d71ec48baad29d7c1ceb9a5a3
Source dataset
uspto-grants-2014_12
Patent number
US08901156B2

Linked notes

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