Pyridine → 2-(3,4-Dichlorophenyl)-N-methoxy-N-methylacetamide

HRID 440887Notes

Reaction equation

HRID 440887 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([OH:12])=O)[CH:5]=[CH:6][C:7]=1[Cl:8].C(Cl)(=O)C(Cl)=O.Cl.[CH3:20][NH:21][O:22][CH3:23].N1C=CC=CC=1>C(Cl)Cl.CN(C)C=O.O>[CH3:23][O:22][N:21]([CH3:20])[C:10](=[O:12])[CH2:9][C:4]1[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=1

Participants

8

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 798743,4-Dichlorophenylacetic acidHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)

Product 1

HCID 152789332-(3,4-Dichlorophenyl)-N-methoxy-N-methylacetamideYield 79.8%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 20.3 grams (0.098 mole) of 3,4-dichlorophenylacetic acid in 200 mL of methylene chloride was stirred, and 10.7 mL (0.124 mole) of oxalyl chloride was added in one portion, followed by 6 drops of N,N-dimethylformamide. Upon completion of addition, the reaction mixture was stirred at ambient temperature for about 18 hours. After this time, 12.0 grams (0.123 mole) of N,O-dimethylhydroxylamine hydrochloride was added in one portion. The reaction mixture was then cooled to 0° C., and 35.9 mL (0.450 mole) of pyridine was added dropwise during a 45 minute period. Upon completion of addition, the reaction mixture was allowed to warm to ambient temperature, where it was stirred for about 18 hours. The reaction mixture was then diluted with 200 mL of water, and the organic layer was separated. The organic layer was washed with 200 mL of an aqueous solution saturated with sodium chloride. The organic layer was dried with sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residue. The residue was subjected to column chromatography on silica gel. Elution was accomplished using 5% ethyl acetate in methylene chloride, then gradually increasing to 15% ethyl acetate in methylene chloride. The product-containing fractions were combined and concentrated under reduced pressure, yielding 19.4 grams of N-methoxy-N-methyl-3,4-dichlorophenylacetamide. The NMR spectrum was consistent with the proposed structure.

Workup

  1. additionUpon completion of addition
  2. temperatureThe reaction mixture was then cooled to 0° C.
  3. additionUpon completion of addition
  4. temperatureto warm to ambient temperature
  5. stirringwhere it was stirred for about 18 hours
  6. customthe organic layer was separated
  7. washThe organic layer was washed with 200 mL of an aqueous solution saturated with sodium chloride
  8. dry with materialThe organic layer was dried with sodium sulfate
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated under reduced pressure to a residue
  11. washElution
  12. temperaturegradually increasing to 15% ethyl acetate in methylene chloride
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-369d31ccd61947639207d05b3c406bf6
Source dataset
uspto-grants-1996_05
Patent number
US05521190

Reaction notes

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