Methyl acetoacetate → 1-(4-Chloro-2-cyclopropylphenyl)-5-methyl-1H-1,2,3-triazole-4-carboxylic acid

HRID 1478805Notes

Reaction equation

HRID 1478805 reaction equation
[N:1]([C:4]1[CH:9]=[CH:8][C:7]([Cl:10])=[CH:6][C:5]=1[CH:11]1[CH2:13][CH2:12]1)=[N+:2]=[N-:3].O=[C:15]([CH3:21])[CH2:16][C:17]([O:19]C)=[O:18].C[O-].[Na+]>CO.O>[Cl:10][C:7]1[CH:8]=[CH:9][C:4]([N:1]2[C:15]([CH3:21])=[C:16]([C:17]([OH:19])=[O:18])[N:3]=[N:2]2)=[C:5]([CH:11]2[CH2:13][CH2:12]2)[CH:6]=1

Participants

6

Reactant 3

HCID 7757Methyl acetoacetateHCID 10942334Sodium MethoxideHCID 1185132901-Azido-4-chloro-2-cyclopropylbenzene

Product 1

HCID 1185132721-(4-Chloro-2-cyclopropylphenyl)-5-methyl-1H-1,2,3-triazole-4-carboxylic acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a stirred solution of 1-azido-4-chloro-2-cyclopropylbenzene (204 mg, 1.054 mmol) and methyl 3-oxobutanoate (0.341 ml, 3.16 mmol) in MeOH (2 ml) was added sodium methoxide (5M in MeOH) (1.264 ml, 6.32 mmol) dropwise and the mixture was stirred at RT for 2.5 h. The mixture was heated at 50° C. for 5 hrs and then left to stir at RT for 16 hrs. The resulting mixture was diluted with water, extracted with diethylether (×2) and the organic extracts were discarded. To the aqueous layer was added 6M HCl (aq) until acidic and this was extracted with diethyl ether. The organic extracts were dried over MgSO4, filtered and concentrated under reduced pressure to yield the title compound as an orange oil.

Workup

  1. temperatureThe mixture was heated at 50° C. for 5 hrs
  2. waitleft
  3. stirringto stir at RT for 16 hrs
  4. extractionextracted with diethylether (×2)
  5. additionTo the aqueous layer was added 6M HCl (aq) until acidic and
  6. extractionthis was extracted with diethyl ether
  7. dry with materialThe organic extracts were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ef5949e9cd0841fc942f5a541135aa55
Source dataset
uspto-grants-2016_08
Patent number
US09403833B2

Reaction notes

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