Iodoethane → Ethyl 1-Ethyl-3-phenyl-1H-pyrazole-5-carboxylate

HRID 396404Notes

Reaction equation

HRID 396404 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[NH:7][N:8]=[C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:10]=1)=[O:5])[CH3:2].I[CH2:18][CH3:19].[H-].[Li+]>CN(C=O)C>[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH2:18][CH3:19])[N:8]=[C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:10]=1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 6340IodoethaneHCID 62714Lithium hydrideHCID 1386281H-Pyrazole-3-carboxylic acid, 5-phenyl-, ethyl ester

Product 1

HCID 9878122Ethyl 1-Ethyl-3-phenyl-1H-pyrazole-5-carboxylateYield 42.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a 0° C. mixture of the above-prepared 5-phenyl-2H-pyrazole-3-carboxylic acid ethyl ester (350 mg, 1.62 mmoles) and iodoethane (260 μL, 3.23 mmoles) in DMF (3 mL) was added neat LiH (spatula tip, excess) under a nitrogen atmosphere. The resulting mixture was warmed up to room temperature and stirred overnight. The crude reaction was cooled to 0° C., quenched with aqueous NH4Cl, diluted with ethyl acetate and enough water to dissolve all solids. The phases were separated, and the organic phase was washed sequentially with water and brine, dried over Na2SO4, filtered, and concentrated in vacuo. The regioisomeric products separated and purified by flash chromatography (silica gel, hexanes/ethyl acetate gradient) to give the title compound (167 mg, 42% yield, higher Rf in hexanes/ethyl acetate) and the undesired regioisomer (175 mg, 44% yield) as white solids. 1H NMR (CDCl3, 400 MHz): 7.81 (d, 2H); 7.40 (dd, 2H); 7.29 (dd, 1H); 7.13 (s, 1H); 4.63 (q, 2H); 4.37 (q, 2H); 1.47 (t, 3H); 1.41 (t, 3H).

Workup

  1. customThe crude reaction
  2. temperaturewas cooled to 0° C.
  3. customquenched with aqueous NH4Cl
  4. additiondiluted with ethyl acetate and enough water
  5. dissolutionto dissolve all solids
  6. customThe phases were separated
  7. washthe organic phase was washed sequentially with water and brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe regioisomeric products separated
  12. custompurified by flash chromatography (silica gel, hexanes/ethyl acetate gradient)

Sources & evidence

ORD record
ord-b0c5f45561e240b0b0cf4d765eb942c3
Source dataset
uspto-grants-2003_08
Patent number
US06608087B1

Reaction notes

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