Isonicotinic Acid → N-Methoxy-N-methylisonicotinamide

HRID 1498876Notes

Reaction equation

HRID 1498876 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([C:7]([OH:9])=O)=[CH:3][CH:2]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.Cl.[CH3:23][NH:24][O:25][CH3:26]>C(Cl)Cl>[CH3:26][O:25][N:24]([CH3:23])[C:7]([C:4]1[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=1)=[O:9]

Participants

5

Reactant 3

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

Product 1

HCID 3817473N-Methoxy-N-methylisonicotinamideYield 61%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a suspension of 4-pyridinecarboxylic acid (12.3 g, 100 mmol) over CH2Cl2 (200 mL) a solution of CDI (18.0 g, 111 mmol) in CH2Cl2 (200 mL) was added. After addition, the mixture was stirred for 2 h at room temperature. Following this, N,O-dimethylhydroxyl-amine hydrochloride (13.9 g, 145 mmol) was added and the mixture was stirred overnight. The reaction mixture was quenched with 1N NaOH and the phases separated. The organic layer was dried over Na2SO4 and concentrated. The crude product was purified by column chromatography (PE/EtOAc=1:1) to give the title compound as orange oil (10.1 g, 61% yield). LC-MS (Method A): m/z 167 (M+H)+, Rt: 0.49 min. 1H NMR (400 MHz, CDCl3): δ=8.64 (d, J=6.0 Hz, 2H), 7.46 (d, J=6.0 Hz, 2H), 3.47 (s, 3H), 3.30 (s, 3H).

Workup

  1. additionwas added
  2. additionAfter addition
  3. additionwas added
  4. stirringthe mixture was stirred overnight
  5. customThe reaction mixture was quenched with 1N NaOH
  6. customthe phases separated
  7. dry with materialThe organic layer was dried over Na2SO4
  8. concentrationconcentrated
  9. customThe crude product was purified by column chromatography (PE/EtOAc=1:1)

Sources & evidence

ORD record
ord-bcca648e3f84441bb56a4a16c519022f
Source dataset
uspto-grants-2015_12
Patent number
US09200005B2

Reaction notes

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