Hydrochloric Acid → N-methoxy-N,3-dimethyl-1-benzofuran-2-carboxamide

HRID 2091003Notes

Reaction equation

HRID 2091003 reaction equation
[CH3:1][C:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][C:3]=1[C:11]([OH:13])=O.Cl.[CH3:15][NH:16][O:17][CH3:18].O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.Cl>C(N(CC)CC)C.CN(C)C=O>[CH3:18][O:17][N:16]([CH3:15])[C:11]([C:3]1[O:4][C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=2[C:2]=1[CH3:1])=[O:13]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)2×HCID 6005913-Methyl-1-benzofuran-2-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 27960291-Hydroxybenzotriazole hydrate2×

Product 1

HCID 55027902N-methoxy-N,3-dimethyl-1-benzofuran-2-carboxamideYield 87%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent2×

Procedure

To a mixture of 3-methyl-1-benzofuran-2-carboxylic acid (15.0 g), N,O-dimethylhydroxyamine hydrochloride (9.95 g), 1-hydroxybenzotriazole-monohydrate (15.6 g), triethylamine (14.2 mL) and N,N-dimethylformamide (150 mL) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (19.6 g), and the mixture was stirred overnight at room temperature. In addition, N,O-dimethylhydroxyamine hydrochloride (4.16 g), 1-hydroxybenzotriazole-monohydrate (6.52 g), triethylamine (5.94 mL) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (8.17 g) were added, and the mixture was stirred at room temperature for 4 hr. 1N Hydrochloric acid was added to quench the reaction, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=3:7, volume ratio) to give the title object compound (16.2 g, 87%) as a colorless oil.

Workup

  1. stirringthe mixture was stirred at room temperature for 4 hr
  2. customto quench
  3. customthe reaction
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe extract was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=3:7, volume ratio)

Sources & evidence

ORD record
ord-98439bfcc37d4530a540922440286cbf
Source dataset
uspto-grants-2013_05
Patent number
US08436043B2

Reaction notes

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