Isopropyl iodide → ethyl 1-isopropyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxylate

HRID 1098571Notes

Reaction equation

HRID 1098571 reaction equation
[CH:1](I)([CH3:3])[CH3:2].[F:5][C:6]([F:18])([F:17])[C:7]1[C:11]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:10][NH:9][N:8]=1.CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C.CN(C)C1C=CN=CC=1>[CH:1]([N:9]1[CH:10]=[C:11]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:7]([C:6]([F:5])([F:17])[F:18])=[N:8]1)([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 6362Isopropyl iodide2×HCID 81531Diisopropylethylamine2×HCID 178469923HCID 178469923, compound

Product 1

HCID 57574507ethyl 1-isopropyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxylateYield 44.3%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
60 °C

Procedure

Isopropyl iodide (1.225 g, 7.21 mmol) was added to a solution of ethyl 3-(trifluoromethyl)-1H-pyrazole-4-carboxylate (500 mg, 2.402 mmol) and DIEA (652 mg, 5.04 mmol) in DMF (5 mL) and the reaction stirred at RT for 3 h and 60° C. for 3 h. The reaction was diluted with ethyl acetate (30 mL), washed with 5% citric acid (30 mL), saturated sodium bicarbonate (30 mL) and brine (30 mL), dried (Na2SO4) and concentrated in vacuo to give an oil. LC and LCMS showed starting material still present (˜40%). The oil was dissolved in DMF (4 mL), treated with DIEA (652 mg, 5.04 mmol), isopropyliodide (1.22 g, 7.21 mmol) and catalytic 4-dimethylaminopyridine (˜5 mg) and stirred at RT overnight. The reaction was diluted with ethyl acetate (30 mL), washed with 5% citric acid (30 mL) saturated sodium bicarbonate (30 mL) and brine (30 mL), dried Na2SO4), concentrated in vacuo and purified by column chromatography (ethyl acetate/hexane) to afford ethyl 1-isopropyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxylate (266 mg, 44% yield). 1H NMR (300 MHz, DMSO-d6): δ 1.26 (s, 9 H), 1.43 (d, 6 H), 4.23 (q, 2 H), 4.64 (hp, 1 H), 8.62 (s, 1 H); MS (ESI) m/z: 251.0 (M+H+).

Workup

  1. washwashed with 5% citric acid (30 mL), saturated sodium bicarbonate (30 mL) and brine (30 mL)
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. customto give an oil
  5. stirringstirred at RT overnight
  6. washwashed with 5% citric acid (30 mL) saturated sodium bicarbonate (30 mL) and brine (30 mL), dried Na2SO4),
  7. concentrationconcentrated in vacuo
  8. custompurified by column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-cb149b8c9bc8439baa2f45dcc1e5c1cb
Source dataset
uspto-grants-2012_03
Patent number
US08143293B2

Reaction notes

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