Toluene → Methyl 3-(5-amino-1,3,4-thiadiazol-2-yl)propanoate

HRID 1951224Notes

Reaction equation

HRID 1951224 reaction equation
[CH3:1][O:2][C:3](=[O:9])[CH2:4][CH2:5][C:6](Cl)=O.[NH2:10][NH:11][C:12]([NH2:14])=O.C1(C)C=CC=CC=1.C[S:23](O)(=O)=O>C1COCC1>[CH3:1][O:2][C:3](=[O:9])[CH2:4][CH2:5][C:6]1[S:23][C:12]([NH2:14])=[N:11][N:10]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 5196SemicarbazideHCID 6395Methanesulfonic AcidHCID 73888Butanoic acid, 4-chloro-4-oxo-, methyl ester

Product 1

HCID 54474128Methyl 3-(5-amino-1,3,4-thiadiazol-2-yl)propanoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3-Chlorocarbonyl-propionic acid methyl ester (4.4 g, 29 mmol) is added dropwise to a stirred suspension of semicarbazide (4.0 g, 44 mmol) in THF (25 ml) at 0° C. After stirring at room temperature for 1 hour, the solvent is removed to give a white solid. Toluene (30 ml) is added followed by dropwise addition of methane sulfonic acid (3.37 ml, 52 mmol) then the reaction is heated at 70° C. for 3 hours. The mixture is concentrated in vacuo and methanol (30 ml) is added. Aqueous ammonia is then added with stirring until a basic mixture is obtained. The solvents are removed and the residue is purified by chromatography on silica eluting with chloroform:methanol (10:1) to give the titled product.

Workup

  1. customthe solvent is removed
  2. customto give a white solid
  3. temperaturethe reaction is heated at 70° C. for 3 hours
  4. concentrationThe mixture is concentrated in vacuo and methanol (30 ml)
  5. additionis added
  6. additionAqueous ammonia is then added
  7. stirringwith stirring until a basic mixture
  8. customis obtained
  9. customThe solvents are removed
  10. customthe residue is purified by chromatography on silica eluting with chloroform:methanol (10:1)

Sources & evidence

ORD record
ord-647acaa8f48342fbba7659aaa47f6dec
Source dataset
uspto-grants-2013_03
Patent number
US08404684B2

Reaction notes

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