Acetic Anhydride → Methyl 1-acetyl-1H-thieno[3,2-c]pyrazole-5-carboxylate

HRID 2078700Notes

Reaction equation

HRID 2078700 reaction equation
[C:1]([O-:4])(=O)[CH3:2].[K+].[CH3:6][O:7][C:8]([C:10]1[S:11][C:12]([CH3:16])=[C:13]([NH2:15])[CH:14]=1)=[O:9].C(OC(=O)C)(=O)C.[N:24](OCCC(C)C)=O>C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH3:6][O:7][C:8]([C:10]1[S:11][C:12]2[CH:16]=[N:24][N:15]([C:1](=[O:4])[CH3:2])[C:13]=2[CH:14]=1)=[O:9]

Participants

7

Reactant 4

HCID 7918Acetic AnhydrideHCID 8053Isoamyl NitriteHCID 517044Potassium AcetateHCID 59640747Methyl 4-amino-5-methylthiophene-2-carboxylate2×

Product 1

HCID 57637373Methyl 1-acetyl-1H-thieno[3,2-c]pyrazole-5-carboxylateYield 49.3%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
93 °C

Procedure

A magnetically stirred mixture of potassium acetate (4.52 g, 46.1 mM) in toluene (100 mL) containing 4-amino-5-methyl-thiophene-2-carboxylic acid methyl ester [12.8 g, 74.7 mM, Intermediate (24)] is warmed to dissolve the amine. Acetic anhydride (13.8 mL, 124.9 mM) is added to this mixture and it is heated in an oil bath. Isoamyl nitrite (9.73 mL, 72.4 mM) is added over 30 minutes. Heating at 93° C. is continued overnight. The cooled mixture is diluted with ethyl acetate (100 mL), filtered and the filtrate is concentrated to a black solid which is purified by chromatography, eluting with heptane-25% ethyl acetate, heptane-35% ethyl acetate, heptane-40% ethyl acetate, heptane-50% ethyl acetate, heptane-60% ethyl acetate. Fractions containing pure product are combined and concentrated to afford 1-acetyl-1H-thieno[3,2-c]pyrazole-5-carboxylic acid methyl ester [9.74 g, 49.3%, Intermediate (25)].

Workup

  1. temperatureis warmed
  2. temperatureis heated in an oil bath
  3. filtrationfiltered
  4. concentrationthe filtrate is concentrated to a black solid which
  5. customis purified by chromatography
  6. washeluting with heptane-25% ethyl acetate, heptane-35% ethyl acetate, heptane-40% ethyl acetate, heptane-50% ethyl acetate, heptane-60% ethyl acetate
  7. additionFractions containing pure product
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-089613941513461496046b80ad397204
Source dataset
uspto-grants-2011_04
Patent number
US07928231B2

Reaction notes

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