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 2199124Notes

Reaction equation

HRID 2199124 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
11 °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 11° 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. concentrationThe reaction mixture was then concentrated under vacuum
  2. additionThe resulting residue was diluted with ethyl acetate (25 mL) and water (20 mL)
  3. additionwas treated with sodium bisulfite (100 mg)
  4. stirringThe resulting mixture was shaken
  5. customThe aqueous layer was separated
  6. extractionwas re-extracted with ethyl acetate (25 mL)
  7. washwashed with a saturated aqueous sodium chloride solution
  8. customThe organic layer was separated
  9. dry with materialdried with sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under vacuum
  12. customThe resulting solid was recrystallized from ethyl acetate
  13. customdried under vacuum overnight

Sources & evidence

ORD record
ord-3b92b59bce5b45ca98dafd27a48aecf8
Source dataset
uspto-grants-2016_06
Patent number
USRE046024E1

Reaction notes

Loading…