Toluene → ethyl 1-cyclopropyl-3-methyl-1H-pyrazole-5-carboxylate

HRID 873824Notes

Reaction equation

HRID 873824 reaction equation
[CH:1]1([NH:4][NH2:5])[CH2:3][CH2:2]1.[C:6]([O:12][CH2:13][CH3:14])(=O)[O:7]COC.[C:15]1(C)[CH:20]=CC=[CH:17][CH:16]=1>CCO>[CH:1]1([N:4]2[C:20]([C:6]([O:12][CH2:13][CH3:14])=[O:7])=[CH:15][C:16]([CH3:17])=[N:5]2)[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 1140TolueneHCID 19594968CyclopropylhydrazineHCID 23565620Ethyl methoxymethyl carbonate

Product 1

HCID 117702822ethyl 1-cyclopropyl-3-methyl-1H-pyrazole-5-carboxylateYield 34%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of cyclopropylhydrazine (Step 17.2) (4.90 g, 45.1 mmol) in toluene (30 mL) and EtOH (30 mL) was added ethyl 2,4-dioxavalerate (6.34 mL, 45.1 mmol). The reaction mixture was stirred for 1 hr at 100° C., quenched with a saturated aq. NaHCO3 solution, and extracted with EtOAc. The combined organic layers were washed with a saturated aq. NaHCO3 solution, dried over Na2SO4 and evaporated. The crude material was purified by silica gel column chromatography (hexane/EtOAc 2.5-30%) to afford the title product (3.01 g, 15.50 mmol, 34% yield). tR: 4.70 min (HPLC 1); tR: 1.01 min (LC-MS 2); ESI-MS: 195 [M+H]+ (LC-MS 2); Rf=0.33 (hexane/EtOAc 9:1).

Workup

  1. customquenched with a saturated aq. NaHCO3 solution
  2. extractionextracted with EtOAc
  3. washThe combined organic layers were washed with a saturated aq. NaHCO3 solution
  4. dry with materialdried over Na2SO4
  5. customevaporated
  6. customThe crude material was purified by silica gel column chromatography (hexane/EtOAc 2.5-30%)

Sources & evidence

ORD record
ord-29e6dac029ce489eb150e45fbea933b4
Source dataset
uspto-grants-2015_03
Patent number
US08975417B2

Reaction notes

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