Hydrochloric Acid → 1-(2-ethoxyethyl)-4-iodo-1H-pyrazole

HRID 1959935Notes

Reaction equation

HRID 1959935 reaction equation
[I:1][C:2]1[CH:3]=[N:4][NH:5][CH:6]=1.C(OCN1C2N=CN=C(C3C=NN([CH:29]([O:31][CH2:32][CH3:33])[CH3:30])C=3)C=2C=C1)(=O)C(C)(C)C.Cl.C([O-])(O)=O.[Na+]>O1CCOCC1.C1(C)C=CC=CC=1>[CH2:29]([O:31][CH2:32][CH2:33][N:4]1[CH:3]=[C:2]([I:1])[CH:6]=[N:5]1)[CH3:30]

Participants

7

Reactant 4

HCID 313Hydrochloric Acid2×HCID 770224-IodopyrazoleHCID 516892Sodium BicarbonateHCID 57868870(4-(1-(1-Ethoxyethyl)-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate

Product 1

HCID 644307821-(2-ethoxyethyl)-4-iodo-1H-pyrazoleYield 98%

Reagents, catalysts & solvents 2

HCID 312751,4-DioxaneCatalystHCID 1140TolueneSolvent

Conditions

Temperature
40 °C

Procedure

A 22 L 4-neck flask equipped with an mechanical stirrer, thermowell, N2 inlet and condenser was charged with 4-iodo-1H-pyrazole (14, 1.00 Kg, 5.16 mol) and toluene (10 L) and ethyl vinyl ether (18, 557 g, 740 mL, 7.73 mol, 1.5 equiv) was added. To the suspension 4 M HCl in dioxane (32 mL, 0.128 mol, 0.025 equiv) was added over 5 min with formation of a slightly thicker white suspension. The mixture was heated carefully to 35-40° C. at which point a mild exotherm to about 40° C. occurred with rapid dissolution of all solids to give a clear light yellow solution. The reaction mixture was heated at about 40° C. for an additional 0.5 hr until the GC analysis indicated the reaction was complete. The solution was allowed to cool to 25-30° C. and solid NaHCO3 (108 g, 1.29 mol, 0.25 equiv) was added. The suspension was stirred for 1 hr at room temperature to ensure the complete neutralization of HCl. The mixture was then filtered and the filtrate was concentrated under reduced pressure. The residual liquid was fractionally distilled to afford 1-(ethoxyethyl)-4-iodo-1H-pyrazole (20, 1.346 Kg, 1.373 Kg theoretical, 98%) as a pale yellow liquid (bp 89-93° at about 1 torr). For 20: 1H NMR (CDCl3, 250 MHz) δ ppm 7.61 (s, 1H), 7.47 (s, 1H), 5.46 (q, 1H, J=6.0 Hz), 3.48-3.23 (m, 2H), 1.60 (d, 3H, J=6.0 Hz), 1.11 (t, 3H, J=7.0 Hz); C7H11IN2O (MW, 266.08), LCMS (EI) m/e 267 (M++H).

Workup

  1. customA 22 L 4-neck flask equipped with an mechanical stirrer
  2. additionwas added
  3. dissolutionoccurred with rapid dissolution of all solids
  4. customto give a clear light yellow solution
  5. temperatureThe reaction mixture was heated at about 40° C. for an additional 0.5 hr until the GC analysis
  6. temperatureto cool to 25-30° C.
  7. filtrationThe mixture was then filtered
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. distillationThe residual liquid was fractionally distilled

Sources & evidence

ORD record
ord-1e8b14d8946449b39cce48a3ac6989c5
Source dataset
uspto-grants-2013_04
Patent number
US08410265B2

Reaction notes

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