Hydrochloric Acid → HCID 22922638, compound

HRID 2258570Notes

Reaction equation

HRID 2258570 reaction equation
O.NN.[F:4][C:5]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][C:6]=1/[CH:13]=[CH:14]/[CH2:15][N:16]1C(=O)C2C(=CC=CC=2)C1=O.Cl>CCO>[F:4][C:5]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][C:6]=1/[CH:13]=[CH:14]/[CH2:15][NH2:16]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 24654Hydrazine hydrate (1:1)HCID 22922657HCID 22922657, compound

Product 1

HCID 22922638HCID 22922638, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
0 °C

Procedure

Hydrazine hydrate (88%)(358 mg, 6.3 mmol) was slowly added to a stirring solution of trans - 2-[3-(2-fluoro-5-methoxyphenyl)prop-2-en-1-yl]-isoindole-1,3-dione (650 mg, 2.1 mmol) in EtOH (40 mL) and the solution was heated to reflux for 5h. The resulting mixture was made acidic (pH<2.0) (10N HCl) followed by heating on a steam bath for 60 min. Cooling of the suspension to 0° C. precipitated the hydrazide which was filtered off, the filtrate was then diluted with H2O (20 mL) and extracted with EtOAc(2×). The aqueous layer was made basic (50% NaOH), and extracted with Et2O (3×). The ethereal layers were combined, washed with brine, dried over MgSO4, and concentrated to give a crude white wax. Purification by Kugelrohr distillation afforded the titled compound as a clear oil, 380 mg, quantitative: 1H NMR (300 MHz, CDCl3) δ 1.49 (s, 2H, br), 3.43 (m, 2H), 3.71 (s, 3H), 5.75 (m, 1H), 6.28 (d, J=11.4 Hz, 1H), 6.65 (m, 2H), 6.90 (m, 1H).

Workup

  1. temperaturethe solution was heated
  2. temperatureto reflux for 5h
  3. temperatureby heating on a steam bath for 60 min
  4. customprecipitated the hydrazide which
  5. filtrationwas filtered off
  6. additionthe filtrate was then diluted with H2O (20 mL)
  7. extractionextracted with EtOAc(2×)
  8. extractionextracted with Et2O (3×)
  9. washwashed with brine
  10. dry with materialdried over MgSO4
  11. concentrationconcentrated
  12. customto give a crude white wax
  13. customPurification
  14. distillationby Kugelrohr distillation

Sources & evidence

ORD record
ord-4166d19182b44bc0a3c68bb77b1a06bf
Source dataset
uspto-grants-1997_08
Patent number
US05661185

Reaction notes

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