Sodium hydride → 5-(4-methoxybutyl)-1-(2-methylphenyl)-1H-1,2,3-triazole-4-carboxylic acid

HRID 1509599Notes

Reaction equation

HRID 1509599 reaction equation
[H-].[Na+].[CH3:3][O:4][CH2:5][CH2:6][CH2:7][CH2:8][C:9](=O)[CH2:10][C:11]([O:13]C)=[O:12].[N:16]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[CH3:25])=[N+:17]=[N-:18]>CN(C=O)C>[CH3:3][O:4][CH2:5][CH2:6][CH2:7][CH2:8][C:9]1[N:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[CH3:25])[N:17]=[N:18][C:10]=1[C:11]([OH:13])=[O:12]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1416521-Azido-2-methylbenzeneHCID 58355424Methyl 7-methoxy-3-oxoheptanoate

Product 1

HCID 583554015-(4-methoxybutyl)-1-(2-methylphenyl)-1H-1,2,3-triazole-4-carboxylic acidYield 45.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of sodium hydride (60% in oil, 280 mg) in DMF (10 ml) was cooled to 0° C.-5° C., methyl 7-methoxy-3-oxoheptanoate (1.32 g) was added, and the mixture was stirred at 0° C.-5° C. for 30 min. Then, 1-azido-2-methylbenzene (932 mg) was added, and the mixture was stirred at room temperature for 15 hr. The solvent was concentrated under reduced pressure, methanol (10 ml) was added to the residue, and 4N aqueous sodium hydroxide solution (5 ml) was added and the mixture was stirred at 60° C. for 1 hr. The solvent was evaporated under reduced pressure and water (20 ml) was added to the residue. 6N Hydrochloric acid was added for neutralization and the mixture was extracted with ethyl acetate (20 ml×2). The extract was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, and a fraction eluted with ethyl acetate was concentrated under reduced pressure to give the object product (930 mg) as an oil.

Workup

  1. stirringthe mixture was stirred at room temperature for 15 hr
  2. concentrationThe solvent was concentrated under reduced pressure, methanol (10 ml)
  3. additionwas added to the residue, and 4N aqueous sodium hydroxide solution (5 ml)
  4. additionwas added
  5. stirringthe mixture was stirred at 60° C. for 1 hr
  6. customThe solvent was evaporated under reduced pressure and water (20 ml)
  7. additionwas added to the residue
  8. addition6N Hydrochloric acid was added for neutralization
  9. extractionthe mixture was extracted with ethyl acetate (20 ml×2)
  10. dry with materialThe extract was dried over anhydrous sodium sulfate
  11. customthe solvent was evaporated under reduced pressure
  12. washa fraction eluted with ethyl acetate
  13. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-e692b934f7614b5b8b1647a9a3a675de
Source dataset
uspto-grants-2015_12
Patent number
US09221836B2

Reaction notes

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