6-[2,6-Dichloro-4-(2-hydroxy-ethyl)-phenoxy]-4-isopropyl-2-methyl-pyridazin-3-one → [3,5-Dichloro-4-(5-isopropyl-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-phenyl]-acetic acid

HRID 271177Notes

Reaction equation

HRID 271177 reaction equation
[Cl:1][C:2]1[CH:19]=[C:18]([CH2:20][CH2:21][OH:22])[CH:17]=[C:16]([Cl:23])[C:3]=1[O:4][C:5]1[CH:6]=[C:7]([CH:13]([CH3:15])[CH3:14])[C:8](=[O:12])[N:9]([CH3:11])[N:10]=1.CC(C)=[O:26].OS(O)(=O)=O.O=[Cr](=O)=O>CC(C)=O>[Cl:1][C:2]1[CH:19]=[C:18]([CH2:20][C:21]([OH:26])=[O:22])[CH:17]=[C:16]([Cl:23])[C:3]=1[O:4][C:5]1[CH:6]=[C:7]([CH:13]([CH3:15])[CH3:14])[C:8](=[O:12])[N:9]([CH3:11])[N:10]=1

Participants

4

Reactant 2

HCID 598344796-[2,6-Dichloro-4-(2-hydroxy-ethyl)-phenoxy]-4-isopropyl-2-methyl-pyridazin-3-oneHCID 131709961Jones' reagent

Product 1

HCID 15981239[3,5-Dichloro-4-(5-isopropyl-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-phenyl]-acetic acidYield 19%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
10 °C

Procedure

A solution of 6-[2,6-dichloro-4-(2-hydroxy-ethyl)-phenoxy]-4-isopropyl-2-methyl-pyridazin-3-one (36) (330 mg, 0.92 mmol) in acetone (5 mL) was treated with Jones Reagent (0.51 mL of a 2.7M solution,) slowly dropwise at 10° C. The resulting red reaction mixture was stirred at 10° C. for 30 min. The reaction mixture was then concentrated under vacuum. The resulting residue was diluted with ethyl acetate (25 mL) and water (20 mL) and was treated with sodium bisulfite (100 mg). The resulting mixture was shaken and turned from red to green. The aqueous layer was separated and was re-extracted with ethyl acetate (25 mL). The organic layers were combined and washed with a saturated aqueous sodium chloride solution. The organic layer was separated, dried with sodium sulfate, filtered, and concentrated under vacuum. The resulting solid was recrystallized from ethyl acetate and dried under vacuum overnight to afford [3,5-dichloro-4-(5-isopropyl-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-phenyl]-acetic acid (37) (70 mg, 19%) as a white solid; EI(+)-HRMS) m/z calcd for C16H16Cl2N2O4 (M+H)+ 371.0560, found 371.0561. Molecular Weight=371.2229; Exact Mass=370.0487

Workup

  1. customslowly dropwise at 10° C
  2. concentrationThe reaction mixture was then concentrated under vacuum
  3. additionThe resulting residue was diluted with ethyl acetate (25 mL) and water (20 mL)
  4. additionwas treated with sodium bisulfite (100 mg)
  5. stirringThe resulting mixture was shaken
  6. customThe aqueous layer was separated
  7. extractionwas re-extracted with ethyl acetate (25 mL)
  8. washwashed with a saturated aqueous sodium chloride solution
  9. customThe organic layer was separated
  10. dry with materialdried with sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated under vacuum
  13. customThe resulting solid was recrystallized from ethyl acetate
  14. customdried under vacuum overnight

Sources & evidence

ORD record
ord-ec2f588be1bf4ed490ee46b8a4c5974f
Source dataset
uspto-grants-2008_11
Patent number
US07452882B2

Reaction notes

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