Picolinic acid → N-Methoxy-N-methylpicolinamide

HRID 1921545Notes

Reaction equation

HRID 1921545 reaction equation
CN1CCOCC1.[N:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C:14]([OH:16])=O.ClC(OCC(C)C)=O.Cl.[CH3:26][NH:27][O:28][CH3:29]>ClCCl>[CH3:29][O:28][N:27]([CH3:26])[C:14]([C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][N:8]=1)=[O:16]

Participants

6

Reactant 4

HCID 1018Picolinic acidHCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)

Product 1

HCID 11829796N-Methoxy-N-methylpicolinamideYield 80%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-15 °C

Procedure

N-Methylmorpholine (3.7 ml) is added to a solution of picolinic acid (2.05 g, 16.65 mmol) in anhydrous dichloromethane (50 mL) and cooled to −15° C. Isobutyl chloroformate (2.2 ml, 16.75 mmol) is added thereto, and the mixture is stirred for 15 hr, after which N,O-dimethylhydroxylamine hydrochloride (1.63 g, 16.71 mmol) is added. After 15 min, the cooling bath is removed and stirring is continued at room temperature for 4 hr. The reaction mixture is added to water (50 ml) and extracted with dichloromethane. The organic phases are washed with water and brine and dried over Na2SO4. The residue is chromatographed on silica gel to afford N-methoxy-N-methylpyridine-2-carboxamide as a colorless oil (2.2 g; 80% yield).

Workup

  1. waitAfter 15 min
  2. customthe cooling bath is removed
  3. stirringstirring
  4. waitis continued at room temperature for 4 hr
  5. additionThe reaction mixture is added to water (50 ml)
  6. extractionextracted with dichloromethane
  7. washThe organic phases are washed with water and brine
  8. dry with materialdried over Na2SO4
  9. customThe residue is chromatographed on silica gel

Sources & evidence

ORD record
ord-158eee04be4f4660b7c7f11c04185dc8
Source dataset
uspto-grants-2012_05
Patent number
US08173682B2

Reaction notes

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