Methanol → 2-Benzyl-5-chloro-4-methoxypyridazin-3(2H)-one

HRID 2224235Notes

Reaction equation

HRID 2224235 reaction equation
[CH2:1]([N:8]1[C:13](=[O:14])[C:12](Cl)=[C:11]([Cl:16])[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:17][O-:18].[Na+].CO>O1CCOCC1>[CH2:1]([N:8]1[C:13](=[O:14])[C:12]([O:18][CH3:17])=[C:11]([Cl:16])[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 7224382-Benzyl-4,5-dichloro-2,3-dihydropyridazin-3-oneHCID 10942334Sodium Methoxide

Product 1

HCID 135262132-Benzyl-5-chloro-4-methoxypyridazin-3(2H)-oneYield 78%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a stirred solution of 2-benzyl-4,5-dichloropyridazin-3(2H)-one (73.1 g, 286.6 mmol) in 1,4-dioxane (700 mL) was added 25 wt. % solution of NaOMe in MeOH (72.0 mL, 315 mmol) at RT under argon over 15 min. The resultant dark reaction mixture was stirred at RT for 1.5 h. The solvent was evaporated and to the resultant residue was added water (500 mL). The aqueous mixture was extracted with methylene chloride (4×120 mL). The combined organic layers were washed with water (2×300 mL) and then by saturated aqueous NaCl (2×150 mL). The organic layer was dried over MgSO4, filtered and concentrated to obtain the crude product. This crude product was purified by silica gel column chromatography eluting with 30% EtOAc/hexanes to give the title compound, 2-benzyl-5-chloro-4-methoxypyridazin-3(2H)-one (56.0 g, 78%) as pale yellow oil. HPLC: 3.19 min; MS, M+H=251. 1H NMR (DMSO-d6, 500 MHz): δ 8.05 (1H, s), 7.26-7.34 (5H, m), 5.24 (2H, s), 4.15 (3H, s).

Workup

  1. customThe resultant dark reaction mixture
  2. customThe solvent was evaporated and to the resultant residue
  3. additionwas added water (500 mL)
  4. extractionThe aqueous mixture was extracted with methylene chloride (4×120 mL)
  5. washThe combined organic layers were washed with water (2×300 mL)
  6. dry with materialThe organic layer was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto obtain the crude product
  10. customThis crude product was purified by silica gel column chromatography
  11. washeluting with 30% EtOAc/hexanes

Sources & evidence

ORD record
ord-74966bcb12744b0dbe342d4e8a28588f
Source dataset
uspto-grants-2008_05
Patent number
US07378418B2

Reaction notes

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