Acetic Acid → (r)-2-(3,4-Difluorophenyl)-4-(3-hydroxy-1-butoxy)-5-[4-(methylsulfonyl)phenyl]-3(2h)-pyridazinone

HRID 891429Notes

Reaction equation

HRID 891429 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:9]2[C:14](=[O:15])[C:13]([O:16][CH2:17][CH2:18][C@H:19]([O:21][Si](C(C)(C)C)(C)C)[CH3:20])=[C:12]([C:29]3[CH:34]=[CH:33][C:32](SC)=[CH:31][CH:30]=3)[CH:11]=[N:10]2)[CH:5]=[CH:6][C:7]=1[F:8].[C:37](OO)(=O)C.C(O)(=O)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C1COCC1.[S:69]([O-:73])([O-])(=[O:71])=S.[Na+].[Na+]>CC(C)=O>[F:1][C:2]1[CH:3]=[C:4]([N:9]2[C:14](=[O:15])[C:13]([O:16][CH2:17][CH2:18][C@H:19]([OH:21])[CH3:20])=[C:12]([C:29]3[CH:34]=[CH:33][C:32]([S:69]([CH3:37])(=[O:73])=[O:71])=[CH:31][CH:30]=3)[CH:11]=[N:10]2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

8

Reactant 6

HCID 176Acetic AcidHCID 6585Peracetic AcidHCID 8028TetrahydrofuranHCID 24477Sodium ThiosulfateHCID 2724141Tetrabutylammonium FluorideHCID 68948236(R)-2-(3,4-Difluorophenyl)-4-[3-(tert-butyldimethylsiloxy)-1-butoxy]-5-[4-(methylthio)phenyl]-3(2H)-pyridazinone

Product 1

HCID 54014854(r)-2-(3,4-Difluorophenyl)-4-(3-hydroxy-1-butoxy)-5-[4-(methylsulfonyl)phenyl]-3(2h)-pyridazinoneYield 87%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A stirred solution of the product from step Example 545D(˜2 mmol) in acetone (10 mL) was chilled to 0° C. To this was added 32% peracetic acid in acetic acid solution (1.42 mL, 6 mmol). The reaction mixture was stirred for 1 hour while warming to room temperature. At this point the oxidation was complete, but some of the product's hydroxy group was still silylated so 1M tetrabutylammonium fluoride in THF (4 mL, 4 mmol) was added and stirring was continued for 0.5 hours. The reaction mixture was then treated with 5% aqueous sodium thiosulfate solution (30 mL) for 2 hours. The precipitated product was collected by filtration, washed with water (10 mL) and hexane (10 mL). The solid was stirred in isopropanol (5 mL) for 6 hours then collected by filtration and dried to provide the title compound (0.78 g, 87%). mp 126-129° C.; 1H NMR (300 MHz, CDCl3) δ 1.22 (d, J=6 Hz, 3H), 1.62-1.74 (m, 1H), 1.84-1.94 (m, 1H), 3.16 (s, 3H), 3.30 (s, br, 1H), 4.00-4.10 (m, 1H), 4.20-4.30 (m, 1H), 4.63 (td, J=9.6 Hz, J=4 Hz, 1H), 7.25-7.34 (m, 1H), 7.46-7.52 (m, 1H), 7.56-7.64 (m, 1H), 7.78-7.84 (m, 2H), 7.97 (s, 1H), 8.06-8.12 (m, 2H); MS (DCI/NH3) m/z 468 (M+NH4)+.

Workup

  1. additionwas added
  2. stirringstirring
  3. waitwas continued for 0.5 hours
  4. filtrationThe precipitated product was collected by filtration
  5. washwashed with water (10 mL) and hexane (10 mL)
  6. stirringThe solid was stirred in isopropanol (5 mL) for 6 hours
  7. filtrationthen collected by filtration
  8. customdried

Sources & evidence

ORD record
ord-0306bda94dd14961a95c7cb949c1056d
Source dataset
uspto-grants-2006_02
Patent number
US07001895B2

Reaction notes

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