Water → 1-(5-methoxycarbonyl-4-nitro-2-trifluoromethyl-phenyl)-1H-[1,2,4]triazole-3-carboxylic acid ethyl ester

HRID 2069265Notes

Reaction equation

HRID 2069265 reaction equation
[H-].[Na+].[CH2:3]([O:5][C:6]([C:8]1[N:12]=[CH:11][NH:10][N:9]=1)=[O:7])[CH3:4].[CH3:13][O:14][C:15](=[O:30])[C:16]1[CH:21]=[C:20](F)[C:19]([C:23]([F:26])([F:25])[F:24])=[CH:18][C:17]=1[N+:27]([O-:29])=[O:28].O>CN1CCCC1=O>[CH2:3]([O:5][C:6]([C:8]1[N:12]=[CH:11][N:10]([C:20]2[CH:21]=[C:16]([C:15]([O:14][CH3:13])=[O:30])[C:17]([N+:27]([O-:29])=[O:28])=[CH:18][C:19]=2[C:23]([F:24])([F:26])[F:25])[N:9]=1)=[O:7])[CH3:4]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 589644905-Fluoro-2-nitro-4-trifluoromethyl-benzoic acid methyl esterHCID 178418794HCID 178418794, compound

Product 1

HCID 589644881-(5-methoxycarbonyl-4-nitro-2-trifluoromethyl-phenyl)-1H-[1,2,4]triazole-3-carboxylic acid ethyl esterYield 71.7%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent3×

Conditions

Temperature
2.5 °C

Procedure

A solution of 613 mg (14.0 mmol) of sodium hydride in 10 ml of 1-methyl-2-pyrrolidinone is cooled to 0-5° C. and treated dropwise with a solution of 1.74 g (12.4 mmol) of 1H-[1,2,4]triazole-3-carboxylic acid ethyl ester in 10 ml of 1-methyl-2-pyrrolidinone over 8 minutes. The mixture is stirred for 1 hour at 0-5° C. and a solution of 3.00 g (11.2 mmol) of 5-fluoro-2-nitro4-trifluoromethyl-benzoic acid methyl ester in 10 ml of 1-methyl-2-pyrrolidinone is added. The mixture is allowed to warm slowly to room temperature and stirred for 18 hours under N2. It is poured into water and extracted with ethyl acetate. The organic phase is separated and dried over Na2SO4, filtered and concentrated in vacuo. The residue is purified by flash chromatography (SiO2, hexane/ethyl acetate 1:1) and the mixed fractions are recrystallized in toluene to provide overall 3.12 g (71%) of 1-(5-methoxycarbonyl-4-nitro-2-trifluoromethyl-phenyl)-1H-[1,2,4]triazole-3-carboxylic acid ethyl ester, m.p. 190-192° C.

Workup

  1. temperatureto warm slowly to room temperature
  2. stirringstirred for 18 hours under N2
  3. extractionextracted with ethyl acetate
  4. customThe organic phase is separated
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue is purified by flash chromatography (SiO2, hexane/ethyl acetate 1:1)
  9. customthe mixed fractions are recrystallized in toluene

Sources & evidence

ORD record
ord-622ae247e9844989b4f87996186d57ff
Source dataset
uspto-grants-2012_10
Patent number
US08299085B2

Reaction notes

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