2-Methylbenzoic acid → N-methoxy-N,2-dimethylbenzamide

HRID 1506118Notes

Reaction equation

HRID 1506118 reaction equation
[CH3:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4](O)=[O:5].Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C.Cl.[CH3:33][NH:34][O:35][CH3:36]>C(Cl)(Cl)Cl.O>[CH3:36][O:35][N:34]([CH3:33])[C:4](=[O:5])[C:3]1[CH:7]=[CH:8][CH:9]=[CH:10][C:2]=1[CH3:1]

Participants

7

Reactant 4

HCID 83732-Methylbenzoic acidHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531Diisopropylethylamine2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 11344340N-methoxy-N,2-dimethylbenzamideYield 50%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6212ChloroformSolvent

Procedure

2-Methylbenzoic acid (1.00 g, 7.34 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.69 g, 8.81 mmol) in chloroform (10 mL) stirred with N,N-diisopropylethylamine (1.50 mL, 8.81 mmol) for 10 minutes under cooling with ice and then stirred with N,O-dimethylhydroxylamine hydrochloride (860 mg, 8.81 mmol) and N,N-diisopropylethylamine (1.50 mL, 8.81 mmol) for one day while the temperature was gradually raised to room temperature. After addition of water, the reaction mixture was extracted with chloroform, and the organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/1 (v/v)) to give the title compound as a pale yellow oil (658 mg, yield 50%).

Workup

  1. temperatureunder cooling with ice
  2. extractionthe reaction mixture was extracted with chloroform
  3. washthe organic layer was washed with saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/1 (v/v))

Sources & evidence

ORD record
ord-f332df48841040e29b262f78ae2862ba
Source dataset
uspto-grants-2015_12
Patent number
US09216999B2

Reaction notes

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