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

HRID 908187Notes

Reaction equation

HRID 908187 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])=[S:13].CS(O)(=O)=O>C1COCC1.C1(C)C=CC=CC=1>[CH3:1][O:2][C:3](=[O:9])[CH2:4][CH2:5][C:6]1[S:13][C:12]([NH2:14])=[N:11][N:10]=1

Participants

6

Reactant 3

HCID 6395Methanesulfonic AcidHCID 73888Butanoic acid, 4-chloro-4-oxo-, methyl esterHCID 2723789Thiosemicarbazide

Product 1

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

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

3-Chlorocarbonyl-propionic acid methyl ester (4.4 g, 21 mmol) is added dropwise to a stirred suspension of thiosemicarbazide (4.0 g, 44 mmol) in THF (25 ml) at 0° C. After stirring at room temperature for 18 h the product which precipitates is removed by filtration and washed with diethyl ether. This product (7.1 g, 34 mmol) is suspended in toluene (30 ml) at 0° C. and methane sulfonic acid (3.37 ml, 52 mmol) is added dropwise to the stirred reaction. The reaction is heated at 70° C. for 3 hours then concentrated at reduced pressure. Methanol (30 ml) is added followed by slow addition of aqueous ammonia, with stirring, until the solution is basic. The titled compound which precipitates is removed by filtration and purified by chromatography on silica, eluting with chloroform-methanol (10:1).

Workup

  1. customprecipitates
  2. customis removed by filtration
  3. washwashed with diethyl ether
  4. temperatureThe reaction is heated at 70° C. for 3 hours
  5. concentrationthen concentrated at reduced pressure
  6. additionMethanol (30 ml) is added
  7. additionfollowed by slow addition of aqueous ammonia
  8. stirringwith stirring, until the solution
  9. customThe titled compound which precipitates
  10. customis removed by filtration
  11. custompurified by chromatography on silica
  12. washeluting with chloroform-methanol (10:1)

Sources & evidence

ORD record
ord-0a714bcfb4764588b3f0b05006714a1c
Source dataset
uspto-grants-2011_09
Patent number
US08017608B2

Reaction notes

Loading…