Hydrazine hydrate (1:1) → 6-[4-(3-chloropropoxy)-3,5-difluorophenyl]-2H-pyridazin-3-one

HRID 221834Notes

Reaction equation

HRID 221834 reaction equation
[Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[C:11]([F:12])=[CH:10][C:9]([C:13](=O)[CH3:14])=[CH:8][C:7]=1[F:16].O.[C:18]([OH:22])(=O)[CH:19]=O.O.[NH2:24][NH2:25]>C(O)(=O)C>[Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[C:11]([F:12])=[CH:10][C:9]([C:13]2[CH:14]=[CH:19][C:18](=[O:22])[NH:24][N:25]=2)=[CH:8][C:7]=1[F:16]

Participants

5

Reactant 3

HCID 24654Hydrazine hydrate (1:1)HCID 15620607Glyoxylic acid, monohydrateHCID 596519231-[4-(3-Chloropropoxy)-3,5-difluorophenyl]ethanone

Product 1

HCID 596520366-[4-(3-chloropropoxy)-3,5-difluorophenyl]-2H-pyridazin-3-oneYield 59%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 1-(4-(3-chloropropoxy)-3,5-difluoro-phenyl]ethanone (11 g, 44.7 mmol) and glyoxalic acid monohydrate (4.2 g, 46.5 mmol) in acetic acid (16 mL) was stirred at 100° C. for 4 h. The acetic acid was evaporated at reduced pressure and diluted with water then cooled to 0° C. and neutralized with ammonium hydroxide to pH 8. To this mixture, hydrazine monohydrate (4.3 mL, 86 mmol) was added and heated at 100° C. for 1 h. The reaction was cooled to rt and the solid was filtered, then dried to give a crude product. The crude product was triturated sequentially with 5% aqueous sodium bicarbonate solution and with a mixture of methylene chloride, methanol, ether and hexane to provide relatively pure product. The product was purified by ISCO (120 g silica gel column) chromatography using 2 to 8% methanol in methylene chloride to furnish 6-[4-(3-chloropropoxy)-3,5-difluorophenyl]-2H-pyridazin-3-one (7.9 g, 59%), MS m/z 301 (M+H).

Workup

  1. customThe acetic acid was evaporated at reduced pressure
  2. additiondiluted with water
  3. temperaturethen cooled to 0° C. and neutralized with ammonium hydroxide to pH 8
  4. temperatureheated at 100° C. for 1 h
  5. temperatureThe reaction was cooled to rt
  6. filtrationthe solid was filtered
  7. customdried
  8. customto give a crude product
  9. customThe crude product was triturated sequentially with 5% aqueous sodium bicarbonate solution and with a mixture of methylene chloride, methanol, ether and hexane
  10. customto provide relatively pure product
  11. customThe product was purified by ISCO (120 g silica gel column) chromatography

Sources & evidence

ORD record
ord-5cf83b4e8e0d4801950b4f78705a57f7
Source dataset
uspto-grants-2012_06
Patent number
US08207168B2

Reaction notes

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