Trimethyl orthoformate → ethyl 3-methyl-5-(5-oxo-1H-1,2,4-triazol-4(5H)-yl)thiophene-2-carboxylate

HRID 560801Notes

Reaction equation

HRID 560801 reaction equation
[NH:1]([C:3]([NH:5][C:6]1[S:10][C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[C:8]([CH3:16])[CH:7]=1)=[O:4])[NH2:2].[CH:17](OC)(OC)OC.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(O)C>[CH3:16][C:8]1[CH:7]=[C:6]([N:5]2[C:3](=[O:4])[NH:1][N:2]=[CH:17]2)[S:10][C:9]=1[C:11]([O:13][CH2:14][CH3:15])=[O:12]

Participants

5

Reactant 3

HCID 9005Trimethyl orthoformateHCID 521998p-Toluenesulfonic acid monohydrateHCID 66631914Ethyl 5-(hydrazinecarboxamido)-3-methylthiophene-2-carboxylate

Product 1

HCID 59481255ethyl 3-methyl-5-(5-oxo-1H-1,2,4-triazol-4(5H)-yl)thiophene-2-carboxylateYield 70%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of ethyl 5-(hydrazinecarboxamido)-3-methylthiophene-2-carboxylate (12.80 g, 52.61 mmol), trimethyl orthoformate (6.33 mL, 57.86 mmol) and p-toluenesulfonic acid monohydrate (0.260 g, 1.367 mmol) in ethanol (130 mL) was stirred at reflux for 30 minutes. The reaction mixture was allowed to cool to ambient temperature, and kept at +5° C. for 16 h. The resulting solid was filtered and washed with ethyl acetate. The filtrate was concentrated, and the residue was triturated with ethanol. The combined material was dried to afford the title compound as a cream solid in 70% yield (9.37 g): 1H NMR (300 MHz, DMSO-d6) δ 12.35 (s, 1H), 8.66 (s, 1H), 7.27 (s, 1H), 4.25 (q, J=7.1 Hz, 2H), 2.47 (s, 3H), 1.29 (t, J=7.1 Hz, 3H); MS (ES+) m/z 254.2 (M+1).

Workup

  1. temperatureat reflux for 30 minutes
  2. filtrationThe resulting solid was filtered
  3. washwashed with ethyl acetate
  4. concentrationThe filtrate was concentrated
  5. customthe residue was triturated with ethanol
  6. customThe combined material was dried

Sources & evidence

ORD record
ord-3fff9b4e28a347239c07c2a0c63f6f8f
Source dataset
uspto-grants-2011_11
Patent number
US08063084B2

Reaction notes

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