Citric Acid → HCID 10275672, compound

HRID 381894Notes

Reaction equation

HRID 381894 reaction equation
C([O:4][C:5]1[CH:35]=[CH:34][C:8]([CH2:9][N:10]2[C:15](=[O:16])[C:14]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)=[C:13]([C:24]3[CH:29]=[CH:28][C:27]([S:30]([CH3:33])(=[O:32])=[O:31])=[CH:26][CH:25]=3)[CH:12]=[N:11]2)=[CH:7][CH:6]=1)(=O)C.O.[OH-].[Li+].CO.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1.O>[OH:4][C:5]1[CH:35]=[CH:34][C:8]([CH2:9][N:10]2[C:15](=[O:16])[C:14]([C:17]3[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=3)=[C:13]([C:24]3[CH:29]=[CH:28][C:27]([S:30]([CH3:33])(=[O:32])=[O:31])=[CH:26][CH:25]=3)[CH:12]=[N:11]2)=[CH:7][CH:6]=1

Participants

7

Reactant 4

HCID 311Citric AcidHCID 887MethanolHCID 168937Lithium hydroxide, monohydrateHCID 10051334HCID 10051334, compound

Product 1

HCID 10275672HCID 10275672, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-(4-acetoxybenzyl)-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone (0.2 g, 4.06 mmol) (Example 114) in THF (20 mL) was treated with a solution of lithium hydroxide monohydrate (0.05 g, 1.22 mmol) in water (5 mL). Methanol (2 mL) was added to provide a homogeneous solution which was stirred at room temperature overnight. The reaction mixture was then acidified with 10% aqueous citric acid and extracted with ethyl acetate. The ethyl acetate layer was dried over MgSO4 and filtered. The filtrate was concentrated in vacuo to provide a white foam which was purified by column chromatography (silica gel, 65:35 hexanes/ethyl acetate). Product fractions were combined and concentrated in vacuo. The residue was crystallized from ethyl acetate/hexanes (yield: 195 mg, 70%). mp 225-226° C. 1H NMR (300 MHz, CDCl3) δ 3.05 (s, 3H), 4.86 (s, 1H), 5.33 (s, 2H), 6.80 (d, J=8.5 Hz, 2H), 6.95 (t, J=9 Hz, 2H), 7.15 (dd, J=9 Hz, 5 Hz, 2H), 7.30 (d, J=8.5 Hz, 2H), 7.46 (d, J=8.5 Hz, 2H), 7.83 (s, 1H), 7.87 (d, J=8.5 Hz, 2H). MS (DCI/NH3) m/z 451 (M+H)+. Anal. calc. for C24H19FN2O4S: C, 63.99; H, 4.25; N, 6.22. Found: C, 63.73; H, 4.16; N, 6.11.

Workup

  1. customto provide a homogeneous solution which
  2. extractionextracted with ethyl acetate
  3. dry with materialThe ethyl acetate layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. customto provide a white foam which
  7. customwas purified by column chromatography (silica gel, 65:35 hexanes/ethyl acetate)
  8. concentrationconcentrated in vacuo
  9. customThe residue was crystallized from ethyl acetate/hexanes (yield: 195 mg, 70%)

Sources & evidence

ORD record
ord-aa1c636dc3e24aaf8004f9f178ac081e
Source dataset
uspto-grants-2001_10
Patent number
US06307047B1

Reaction notes

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