Methanol → 2-methoxy-5-(4H-triazol-4-yl)benzoic acid

HRID 609797Notes

Reaction equation

HRID 609797 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[CH:11][C:10]([CH:13]2[CH:17]=[N:16][N:15]=[N:14]2)=[CH:9][C:4]=1[C:5]([O:7]C)=[O:6].CO.[OH-].[Na+]>O>[CH3:1][O:2][C:3]1[CH:12]=[CH:11][C:10]([CH:13]2[CH:17]=[N:16][N:15]=[N:14]2)=[CH:9][C:4]=1[C:5]([OH:7])=[O:6]

Participants

5

Reactant 3

HCID 887MethanolHCID 14798Sodium HydroxideHCID 18464913methyl 2-methoxy-5-(4H-triazol-4-yl)benzoate

Product 1

HCID 184644732-methoxy-5-(4H-triazol-4-yl)benzoic acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Alternately, according to the method of J. Med. Chem., 21, 1100 (1978), combine methyl 2-methoxy-5-aminobenzoate (1.8 g, 10 mmol), diformyl hydrazine (0.97 g, 11 mmol), and phosphorous pentoxide (1.84 g, 13 mmol). Heat to 160° C. After 1.5 hours, cool the reaction mixture and add a saturated aqueous solution of sodium bicarbonate. Extract three times with dichloromethane. Dry the combined organic layers over MgSO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting sequentially with 40% ethyl acetate/dichloromethane and then 5% methanol/dichloromethane to give methyl 2-methoxy-5-(4H-triazol-4-yl)benzoate: mp; 179-182° C. Combine methyl 2-methoxy-5-(4H-triazol-4-yl)benzoate (56 mmol) and methanol (200 mL) and water (50 mL). Add 1 M aqueous solution of sodium hydroxide (62.5 mL, 62.5 mmol). Heat to reflux. After 8 hour, concentrate in vacuo to remove most of the solvent. Adjust the pH to about 1 to 2 using a 1 M aqueous hydrochloric acid solution, extract with dichloromethane. Dry the organic layer over MgSO4, filter, and evaporate invacuo to give 2-methoxy-5-(4H-triazol-4-yl)benzoic acid.

Workup

  1. temperatureHeat to reflux
  2. concentrationconcentrate in vacuo
  3. customto remove most of the solvent
  4. extractionextract with dichloromethane
  5. dry with materialDry the organic layer over MgSO4
  6. filtrationfilter
  7. customevaporate invacuo

Sources & evidence

ORD record
ord-1cb8961177a240389c303f4f968c39a3
Source dataset
uspto-grants-1999_12
Patent number
US05998439

Reaction notes

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