Carbon Dioxide → N-Methoxy-N-methylisonicotinamide

HRID 51275Notes

Reaction equation

HRID 51275 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([C:7]([OH:9])=O)=[CH:3][CH:2]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.C(=O)=O.Cl.[CH3:26][NH:27][O:28][CH3:29]>C(Cl)Cl>[CH3:26][N:27]([O:28][CH3:29])[C:7](=[O:9])[C:4]1[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=1

Participants

6

Reactant 4

HCID 280Carbon DioxideHCID 5922Isonicotinic AcidHCID 682631,1'-CarbonyldiimidazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)

Product 1

HCID 3817473N-Methoxy-N-methylisonicotinamideYield 62.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-pyridinecarboxylic acid (18) (17.0 g, 0.138 mol) is slurried in methylene chloride (200 mL) and treated with 1,1′-carbonyldiimidazole (25 g, 0.154 mol). After a 1 minute induction period, CO2 evolution begins and the solution becomes homogeneous. After stirring at ambient temperature for 2 hours, the solution is treated with N,O-dimethylhydroxylamine hydrochloride (20 g, 0.20 mol) and stirred at room temperature overnight. The reaction mixture is quenched with 1 N NaOH and the phases separated. After a normal work-up, the organic phase is concentrated to leave an oil. Kugelrohr distillation provided the title compound (19) as a clear liquid (14.34 g, 62% yield); b.p. 120-135° C./0.5 mm Hg.

Workup

  1. stirringstirred at room temperature overnight
  2. customThe reaction mixture is quenched with 1 N NaOH
  3. customthe phases separated
  4. concentrationAfter a normal work-up, the organic phase is concentrated
  5. customto leave an oil
  6. distillationKugelrohr distillation

Sources & evidence

ORD record
ord-10e3b87e88034389a9f3e52095d55219
Source dataset
uspto-grants-2004_03
Patent number
US06713627B2

Reaction notes

Loading…