Methyl 5-bromopyridine-3-carboxylate → Methyl 5-cyanopyridine-3-carboxylate

HRID 1397210Notes

Reaction equation

HRID 1397210 reaction equation
[C:1]([Cu])#[N:2].Br[C:5]1[CH:6]=[N:7][CH:8]=[C:9]([CH:14]=1)[C:10]([O:12][CH3:13])=[O:11]>CN(C=O)C>[CH3:13][O:12][C:10](=[O:11])[C:9]1[CH:14]=[C:5]([C:1]#[N:2])[CH:6]=[N:7][CH:8]=1

Participants

4

Reactant 2

HCID 699336Methyl 5-bromopyridine-3-carboxylateHCID 178418546HCID 178418546, compound

Product 1

HCID 13623673Methyl 5-cyanopyridine-3-carboxylateYield 60%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
160 °C

Procedure

CuCN (5.22 g, 58.3 mmol) was added to a solution of methyl 5-bromonicotinate (6 g, 27.8 mmol) in dry DMF (150 mL). The solution was purged with argon and heated to 160° C. for 12 h under argon atmosphere. The reaction mixture was cooled to room temperature and then quenched with saturated NH4Cl solution. Further EtOAc was added and the reaction mixture was stirred for 10 min. The reaction mixture was filtered through a Celite plug, the organic layer was separated, washed with water and brine, and dried over anhydrous Na2SO4. Solvent was evaporated under reduced pressure to get methyl-5-cyano-nicotinate as greenish-white solid (2.7 g, yield 60%): 1H NMR (300 MHz, DMSO-d6) δ 9.29-9.27 (m, 2H), 8.77 (s, 1H), 3.91 (s, 3H)

Workup

  1. customThe solution was purged with argon
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customquenched with saturated NH4Cl solution
  4. additionFurther EtOAc was added
  5. filtrationThe reaction mixture was filtered through a Celite plug
  6. customthe organic layer was separated
  7. washwashed with water and brine
  8. dry with materialdried over anhydrous Na2SO4
  9. customSolvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-4cb7857aeb2845b88f695829cfa74ae7
Source dataset
uspto-grants-2014_12
Patent number
US08901156B2

Reaction notes

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