Sodium Acetate → HCID 73854757, compound

HRID 891394Notes

Reaction equation

HRID 891394 reaction equation
[CH2:1]([N:10]1[C:15](=[O:16])[C:14]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)=[C:13]([C:24]2[CH:29]=[CH:28][C:27]([S:30]([CH3:33])(=[O:32])=[O:31])=[CH:26][CH:25]=2)[CH:12]=[N:11]1)[C:2]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)=O.Cl.[O:35]([NH2:37])[CH3:36].C([O-])(=O)C.[Na+]>CO>[CH3:36][O:35][N:37]=[C:2]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[CH2:1][N:10]1[C:15](=[O:16])[C:14]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)=[C:13]([C:24]2[CH:25]=[CH:26][C:27]([S:30]([CH3:33])(=[O:32])=[O:31])=[CH:28][CH:29]=2)[CH:12]=[N:11]1

Participants

5

Reactant 3

HCID 517045Sodium AcetateHCID 521874O-Methylhydroxylamine hydrochlorideHCID 10183161HCID 10183161, compound2×

Product 1

HCID 73854757HCID 73854757, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of the product from Example 46, 2-phenacyl-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone (220 mg, 0.476 mmol), methoxylamine hydrochloride (318 mg, 3.8 mmol), and sodium acetate (518 mg, 3.8 mmol) in methanol (100 mL) was stirred at reflux for 48 hours. The reaction mixture was concentrated in vacuo, and the residue was partitioned between ethyl acetate and saturated aqueous ammonium chloride. The organic layer was washed with brine then dried over MgSO4, and filtered. The filtrate was concentrated in vacuo to provide a brown oil which was purified by column chromatography (silica gel, 70:30 hexanes/ethyl acetate). Fractions containing product were combined and concentrated in vacuo. The residue was crystallized from methanol/water to provide the title compound as a mixture of E and Z oximes (yield: 82 mg, 35%). mp 95-99° C. 1H NMR (300 MHz, CDCl3) δ 3.03 (s, 3H), 4.07 (s, 3H), 5.57 (s, 2H), 6.94 (t, J=9 Hz, 2H), 7.07 (dd, J=9 Hz, 3 Hz, 2H), 7.24 (d, J=9 Hz, 2H), 7.31-7.37 (m, 3H), 7.60-7.67 (m, 2H), 7.74 (s, 1H), 7.83 (d, J=9 Hz, 2H). MS (DCI/NH3) m/z 492 (M+H)+. Anal. calc. for C26H22FN3O4S: C, 63.53; H, 4.51; N, 8.54. Found: C, 63.40; H, 4.51; N, 8.31.

Workup

  1. temperatureat reflux for 48 hours
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customthe residue was partitioned between ethyl acetate and saturated aqueous ammonium chloride
  4. washThe organic layer was washed with brine
  5. dry with materialthen dried over MgSO4
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo
  8. customto provide a brown oil which
  9. customwas purified by column chromatography (silica gel, 70:30 hexanes/ethyl acetate)
  10. additionFractions containing product
  11. concentrationconcentrated in vacuo
  12. customThe residue was crystallized from methanol/water

Sources & evidence

ORD record
ord-31ccf4fa6a6042b7b97461a911cfca45
Source dataset
uspto-grants-2006_02
Patent number
US07001895B2

Reaction notes

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