Hydrochloric Acid → 4-(2,2,2-Trifluoro-ethoxy)-1H-pyrazole-3,5-dicarboxylic acid diethyl ester

HRID 33275

Reaction equation

HRID 33275 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:10](I)=[C:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[NH:8][N:7]=1)=[O:5])[CH3:2].N1C2C(=CC=C3C=2N=CC=C3)C=CC=1.Cl.[F:32][C:33]([F:37])([F:36])[CH2:34][OH:35]>C(O)C.[Cu]I>[CH2:1]([O:3][C:4]([C:6]1[C:10]([O:35][CH2:34][C:33]([F:37])([F:36])[F:32])=[C:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[NH:8][N:7]=1)=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 13181,10-PhenanthrolineHCID 64092,2,2-TrifluoroethanolHCID 117392303,5-diethyl 4-iodo-1H-pyrazole-3,5-dicarboxylate

Product 1

HCID 574744254-(2,2,2-Trifluoro-ethoxy)-1H-pyrazole-3,5-dicarboxylic acid diethyl ester

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 702EthanolSolvent

Procedure

To a solution of 1 g 4-Iodo-1H-pyrazole-3,5-dicarboxylic acid diethyl ester in 5 ml 2,2,2-trifluoro-ethanol 1.4 g Cs2CO3, 56 mg CuI and 106 mg 1,10-Phenanthroline were added. The reaction mixture heated for 4 h to 100° C. under microwave irradiation (100 W, CEM Discover™ apparatus). Then 10 HCl in ethanol (8M) was added and the solution was stirred at RT. After 16 h the solvents were removed under reduced pressure and the residue taken up in DCM and water. The organic phase was separated and the aqueous layer was extracted with DCM (2×50 ml). The combined organic layers were dried over MgSO4, filtered and the solvent was removed under reduced pressure. The residue was purified by preparative HPLC (C18 reverse phase column, elution with a H2O/MeCN gradient with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to yield a white solid. Yield: 359 mg.

Workup

  1. temperatureThe reaction mixture heated for 4 h to 100° C. under microwave irradiation (100 W, CEM Discover™ apparatus)
  2. customAfter 16 h the solvents were removed under reduced pressure
  3. customThe organic phase was separated
  4. extractionthe aqueous layer was extracted with DCM (2×50 ml)
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. filtrationfiltered
  7. customthe solvent was removed under reduced pressure
  8. customThe residue was purified by preparative HPLC (
  9. washC18 reverse phase column, elution with a H2O/MeCN gradient with 0.1% TFA)
  10. additionThe fractions containing the product
  11. customwere evaporated
  12. customto yield a white solid

Sources & evidence

ORD record
ord-f62670b42552435cbab75bf3e1bab8a4
Source dataset
uspto-grants-2008_09
Patent number
US07429581B2

Linked notes

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