Nicotinic Acid → N-Methoxy-N-methylnicotinamide

HRID 1661553Notes

Reaction equation

HRID 1661553 reaction equation
[C:1]([OH:9])(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1.S(Cl)(Cl)=O.[CH3:14][O:15][NH:16][CH3:17].C(N(CC)CC)C>>[CH3:17][N:16]([O:15][CH3:14])[C:1](=[O:9])[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1

Participants

5

Reactant 4

HCID 938Nicotinic AcidHCID 8471TriethylamineHCID 14232N,O-DimethylhydroxylamineHCID 24386Thionyl Chloride

Product 1

HCID 10558996N-Methoxy-N-methylnicotinamide

Procedure

A flask is charged with nicotinic acid (5.0 g, 40.6 mmol). Thionyl chloride (30.0 mL) is added and the reaction is refluxed for 1 h. It is then cooled to room temperature and concentrated in vacuo. The residue is dissolved in anhydrous dichloromethane (30 mL) and O,N-dimethyl-hydroxylamine (4.35 g, 44.0 mmol) is added, followed by addition of triethylamine (14.15 g, 100.0 mmol). The reaction mixture is stirred at room temperature for 1.5 h. It is then washed with water and the aqueous phase is extracted with dichloromethane. The combined organic layer is dried over sodium sulfate and concentrated in vacuo to afford N-methyl-N-methoxy-nicotinamide as a brown oil. MS (ESI) m/z 167.0 (M+H)+.

Workup

  1. temperaturethe reaction is refluxed for 1 h
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue is dissolved in anhydrous dichloromethane (30 mL)
  4. washIt is then washed with water
  5. extractionthe aqueous phase is extracted with dichloromethane
  6. dry with materialThe combined organic layer is dried over sodium sulfate
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-921d9660561848f1aa7153685e02f075
Source dataset
uspto-grants-2011_10
Patent number
US08030334B2

Reaction notes

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