Isopropyl iodide → Ethyl 5-iodo-1-isopropyl-1H-pyrazole-4-carboxylate

HRID 880897Notes

Reaction equation

HRID 880897 reaction equation
[I:1][C:2]1[C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:5][NH:4][N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].I[CH:19]([CH3:21])[CH3:20]>CN(C)C=O.O>[I:1][C:2]1[N:3]([CH:19]([CH3:21])[CH3:20])[N:4]=[CH:5][C:6]=1[C:7]([O:9][CH2:10][CH3:11])=[O:8]

Participants

6

Reactant 3

HCID 6362Isopropyl iodideHCID 10796Cesium carbonateHCID 178469927HCID 178469927, compound

Product 1

HCID 67491584Ethyl 5-iodo-1-isopropyl-1H-pyrazole-4-carboxylateYield 18.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of ethyl 3-iodopyrazole-4-carboxylate (1.58 g, 5.94 mmol, Truong; et al. Bioorg. Med. Chem. Lett., 19, 4920 (2009)) in 20 mL N,N-dimethylformamide was added cesium carbonate (3.87 g, 11.9 mmol) and 2-iodopropane (0.89 mL, 8.90 mmol). The mixture was stirred 2 hours at 60° C. and then cooled to ambient temperature. The reaction mixture was diluted with 150 mL water and extracted with 2×100 mL diethyl ether. The combined organics were washed with 50 mL brine, dried over sodium sulfate, filtered and concentrated. The resultant oil was purified by flash chromatography (7-60% ethyl acetate/heptane gradient, 50 g silica) to yield 340 mg of ethyl 5-iodo-1-isopropyl-1H-pyrazole-4-carboxylate as a clear oil which crystallized on standing and 740 mg of ethyl 3-iodo-1-isopropyl-1H-pyrazole-4-carboxylate as a clear oil. Ethyl 5-iodo-1-isopropyl-1H-pyrazole-4-carboxylate: +APCI (M+H) 309.0; 1H NMR (400 MHz, CDCl3, δ): 8.05 (s, 1H) 4.82 (spt, J=6.6 Hz, 1H) 4.33 (q, J=7.2 Hz, 2H) 1.50 (d, J=6.6 Hz, 6H) 1.37 (t, J=7.1 Hz, 3H). Ethyl 3-iodo-1-isopropyl-1H-pyrazole-4-carboxylate: +APCI (M+H) 309.0; 1H NMR (400 MHz, CDCl3, δ): 7.84 (s, 1H) 4.52 (spt, J=6.7 Hz, 1H) 4.32 (q, J=7.1 Hz, 2H) 1.52 (d, J=6.6 Hz, 6H) 1.37 (t, J=7.1 Hz, 3H).

Workup

  1. temperaturecooled to ambient temperature
  2. extractionextracted with 2×100 mL diethyl ether
  3. washThe combined organics were washed with 50 mL brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resultant oil was purified by flash chromatography (7-60% ethyl acetate/heptane gradient, 50 g silica)

Sources & evidence

ORD record
ord-1e318e3bf5f84a03a23f5d4806f30e4f
Source dataset
uspto-grants-2015_03
Patent number
US08993586B2

Reaction notes

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