1,2-Dichloroethane → 6-Chloro-N-methoxy-N-methylnicotinamide

HRID 1799176Notes

Reaction equation

HRID 1799176 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](O)=[O:7])=[CH:4][N:3]=1.Cl.[CH3:12]OCN.C(Cl)CCl.C1C=C[C:23]2[N:28]([OH:29])N=NC=2C=1>C(#N)C>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([N:28]([O:29][CH3:12])[CH3:23])=[O:7])=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 792226-Chloronicotinic acidHCID 21959107Methoxymethanamine hydrochloride

Product 1

HCID 114355976-Chloro-N-methoxy-N-methylnicotinamideYield 304.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 6-chloronicotinic acid (20 g, 127 mmol) in acetonitrile (400 mL), methoxymethylamine hydrochloride (13.79 g, 141 mmol), EDC (27.1 g, 141 mmol), HOBT (5.2 g, 38.58 mmol) and TEA (53.3 mL, 386 mmol) were added at RT. The reaction mixture was stirred at RT overnight. Solvent was removed under reduced pressure and the residue was dissolved in ethyl acetate (300 mL). The reaction mixture was washed with water and brine. The organic layer was dried, filtered and concentrated. Purification of the crude product provided 23.6 g (93%) of compound A as viscous colorless oil.

Workup

  1. customSolvent was removed under reduced pressure
  2. dissolutionthe residue was dissolved in ethyl acetate (300 mL)
  3. washThe reaction mixture was washed with water and brine
  4. customThe organic layer was dried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification of the crude product

Sources & evidence

ORD record
ord-b2c37992501d4d57b2004d0e9966a753
Source dataset
uspto-grants-2013_01
Patent number
US08343996B2

Reaction notes

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