Ammonia → HCID 54141266, compound

HRID 1461822Notes

Reaction equation

HRID 1461822 reaction equation
[N:1]([O-])=O.[Na+].[Cl:5][C:6]1[CH:7]=[C:8]([CH:10]=[CH:11][CH:12]=1)[NH2:9].[CH2:13]([O:15][C:16](=[O:22])[CH:17](Cl)C(C)=O)[CH3:14].C([O-])(=O)C.[Na+].[NH3:28].[F:29][C:30]1[CH:38]=[CH:37][CH:36]=[CH:35][C:31]=1[C:32](Cl)=O>O.Cl.C(O)C.O1CCCC1.C1(C)C=CC=CC=1>[CH2:13]([O:15][C:16]([C:17]1[N:1]=[C:32]([C:31]2[CH:35]=[CH:36][CH:37]=[CH:38][C:30]=2[F:29])[N:9]([C:8]2[CH:10]=[CH:11][CH:12]=[C:6]([Cl:5])[CH:7]=2)[N:28]=1)=[O:22])[CH3:14]

Participants

12

Reactant 6

HCID 222AmmoniaHCID 79323-ChloroanilineHCID 98082-Fluorobenzoyl chlorideHCID 11858Ethyl 2-chloroacetoacetateHCID 517045Sodium AcetateHCID 23668193Sodium Nitrite

Product 1

HCID 54141266HCID 54141266, compound

Reagents, catalysts & solvents 5

HCID 313Hydrochloric AcidSolvent2×HCID 702EthanolSolventHCID 962WaterSolvent6×HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 14.0 g (0.202 mol) of sodium nitrite in 80 ml of water is added dropwise, at 0° C., to a suspension of 25.5 g (0.2 mol) of 3-chloroaniline in 80 ml of water and 65 ml of concentrated hydrochloric acid. After stirring for 15 minutes to complete the reaction, the foamy brown solution is poured into a mixture of 33.1 g (0.201 mol) of 2-chloroacetoacetic acid ethyl ester, 90 g of sodium acetate in 160 ml of water and 200 ml of ethanol. The whole is then stirred at 10° C. for 3 hours to complete the reaction. After the addition of 1 liter of water, a red oil separates and is extracted with ethyl acetate. After drying with magnesium sulfate and concentrating the extract there is obtained, in quantitative yield, an orange-red, crystalline material which is dissolved in 320 ml of tetrahydrofuran. 35 g (0.625 mol) of 25% aqueous ammonia are added dropwise at 15°-20° C. and the whole is then stirred for two hours. The end of the reaction is determined by thin-layer chromatography. 1 liter of water is then added and the resulting oil is extracted with ethyl acetate. After drying and concentrating the extract by evaporation, 40.7 g (84.4% of the theoretical yield) of an intermediate are obtained. 4.8 g (0.02 mol) thereof are dissolved in 30 ml of toluene, and 2.5 ml (0.021 mol) of 2-fluorobenzoyl chloride are added thereto. The clear, brown reaction solution is heated until water and hydrochloric acid separate out and the solvent has been distilled off. The residue is subjected to preliminary purification over a short column of silica gel and is then recrystallised from ether/hexane to yield 3.6 g (52.2% of the theoretical yield) of 1-(3-chlorophenyl)-5-(2-fluorophenyl)-1,2,4-triazole-3-carboxylic acid ethyl ester in the form of white-beige crystals melting at 77°-78° C.

Workup

  1. customthe reaction
  2. stirringThe whole is then stirred at 10° C. for 3 hours
  3. customthe reaction
  4. extractiona red oil separates and is extracted with ethyl acetate
  5. dry with materialAfter drying with magnesium sulfate
  6. concentrationconcentrating the
  7. extractionextract there
  8. customis obtained, in quantitative yield
  9. stirringthe whole is then stirred for two hours
  10. extractionthe resulting oil is extracted with ethyl acetate
  11. customAfter drying
  12. concentrationconcentrating the
  13. extractionextract by evaporation, 40.7 g (84.4% of the
  14. customtheoretical yield) of an intermediate
  15. customare obtained
  16. customseparate out
  17. distillationthe solvent has been distilled off
  18. customThe residue is subjected to preliminary purification over a short column of silica gel
  19. customis then recrystallised from ether/hexane
  20. customto yield 3.6 g (52.2% of the

Sources & evidence

ORD record
ord-de088c0e553643d6b0f5622af4e89388
Source dataset
uspto-grants-1991_12
Patent number
US05077413

Reaction notes

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