Triethylamine → 1-[(4-Methoxy)phenyl)-3-(methoxycarbonylamino)-5-(methoxycarbonyl)pyrazole

HRID 610146Notes

Reaction equation

HRID 610146 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][C:11](C(O)=O)=[N:10]2)=[CH:5][CH:4]=1.C([N:23](CC)CC)C.Cl[C:29]([O:31][CH2:32]C(C)C)=[O:30].[N-]=[N+]=[N-].[Na+]>CC(C)=O.C(OCC)(=O)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([N:9]2[C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][C:11]([NH:23][C:29]([O:31][CH3:32])=[O:30])=[N:10]2)=[CH:7][CH:8]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 33557Sodium AzideHCID 62365Isobutyl chloroformateHCID 542100671-[(4-Methoxy)phenyl]-5-(methoxycarbonyl)pyrazole-3-carboxylic acid

Product 1

HCID 541498731-[(4-Methoxy)phenyl)-3-(methoxycarbonylamino)-5-(methoxycarbonyl)pyrazoleYield 33.1%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 1-[(4-methoxy)phenyl]-5-(methoxycarbonyl)pyrazole-3-carboxylic acid (3.0 g, 10.9 mmol) in 50 mL of acetone at 0° C. was added triethylamine (1.66 mL, 11.9 mmol) followed by iso-butyl chloroformate (1.14 mL, 11.9 mmol). The resulting was stirred for 30 min whereupon an aqueous solution of sodium azide (2.82 g, 43.4 mmol) was added. The reaction was stirred at 0° C. for 1 h. The reaction was then diluted with ethyl acetate and washed with brine. The organics were dried (MgSO4) and concentrated in vacuo. The residue was dissolved in 50 mL of toluene and stirred at 100° C. for 1 h. The volatiles were removed in vacuo and the residue was dissolved in methanolic sodium methoxide (5 mL of a 25% solution of sodium methoxide in methanol, 21 mmol) and stirred at ambient temperature for 2 h. The reaction was diluted with ethyl acetate, washed with water and brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by flash chromatography (elution with 1:1 hexanes/ethyl acetate) to afford 1.1 g (33%) of the title compound as a solid. LRMS (DCI): 306.3 (M+H)+.

Workup

  1. additionwas added
  2. washwashed with brine
  3. dry with materialThe organics were dried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was dissolved in 50 mL of toluene
  6. stirringstirred at 100° C. for 1 h
  7. customThe volatiles were removed in vacuo
  8. dissolutionthe residue was dissolved in methanolic sodium methoxide (5 mL of a 25% solution of sodium methoxide in methanol, 21 mmol) and
  9. stirringstirred at ambient temperature for 2 h
  10. additionThe reaction was diluted with ethyl acetate
  11. washwashed with water and brine
  12. dry with materialdried (MgSO4)
  13. concentrationconcentrated in vacuo
  14. customThe residue was purified by flash chromatography (elution with 1:1 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-9b8cc2768d154fd8bf99320a0514aabd
Source dataset
uspto-grants-1999_12
Patent number
US05998424

Reaction notes

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