2,4,6-Trimethylpyridine → 5-chloro-2'-pyridin-4-yl-5',6'-dihydro-3H,7'H-spiro[2-benzofuran-1,4'-[1]benzothiophene]-3,7'-dione

HRID 1615487Notes

Reaction equation

HRID 1615487 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]2[C:8]3([O:23][C:24](=[O:25])[C:4]=2[CH:3]=1)[C:13]1[CH:14]=[C:15]([C:17]2[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=2)[S:16][C:12]=1[CH2:11][CH2:10][CH2:9]3.[O:26]1CCOCC1.S(OOS([O-])(=O)=O)([O-])(=O)=O.[K+].[K+].CC1C=C(C)N=C(C)C=1>O.CCOC(C)=O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Cu+2].C(#N)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]2[C:8]3([O:23][C:24](=[O:25])[C:4]=2[CH:3]=1)[C:13]1[CH:14]=[C:15]([C:17]2[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=2)[S:16][C:12]=1[C:11](=[O:26])[CH2:10][CH2:9]3

Participants

9

Reactant 4

HCID 79532,4,6-Trimethylpyridine2×HCID 24412Potassium Persulfate2×HCID 312751,4-Dioxane2×HCID 681829575-chloro-2'-pyridin-4-yl-6',7'-dihydro-3H,5'H-spiro[2-benzofuran-1,4'-[1]benzothiophen]-3-one

Product 1

HCID 569709015-chloro-2'-pyridin-4-yl-5',6'-dihydro-3H,7'H-spiro[2-benzofuran-1,4'-[1]benzothiophene]-3,7'-dioneYield 3%

Reagents, catalysts & solvents 4

HCID 24463Copper sulfate pentahydrateCatalyst2×HCID 962WaterSolvent2×HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

In a 100 mL round bottomed flask was placed 5-chloro-2′-pyridin-4-yl-6′,7′-dihydro-3H,5′H-spiro[2-benzofuran-1,4′-[1]benzothiophen]-3-one (0.714 g, 1.94 mmol) (including side product) along with 1,4-dioxane (20 mL) and acetonitrile (10 mL). To the mixture was added a suspension of potassium persulfate (1.85 g, 6.84 mmol) and copper (II) sulfate pentahydrate (180 mg, 0.72 mmol) in water (20 mL) followed by γ-collidine (0.897 mL, 6.79 mmol). The mixture was stirred for 3.5 hr at 80° C. Again, to the mixture was added a suspension of potassium persulfate (1.96 g, 7.25 mmol) and copper(II) sulfate pentahydrate (20 mg, 0.08 mmol) in water (20 mL, 1000 mmol) followed by γ-collidine (0.9 mL, 7 mmol) and 1,4-dioxane (10 mL, 100 mmol). The mixture was stirred for an additional 16 hr at 80° C. The mixture was allowed to cool to rt and then diluted with EtOAc (50 mL). Insoluble materials were removed by filtration through a celite pad and the aqueous phase was separated from the filtrate. The aqueous phase was extracted with EtOAc (50 mL). The combined organic phases were dried over anhydrous MgSO4. Insoluble materials were removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by HPLC (FA) to obtain the title compound (22.5 mg; 3%) as an off-white crystalline solid. LCMS: (FA) ES+ 382, 384; 1H NMR (400 MHz, d6-DMSO) δ ppm 8.59 (dd, 2H), 8.07 (d, 1H), 7.89 (dd, 1H), 7.77 (d, 1H), 7.71 (dd, 2H), 7.46 (s, 1H), 2.47-3.05 (m, 4H).

Workup

  1. customIn a 100 mL round bottomed flask was placed
  2. additionTo the mixture was added
  3. additionAgain, to the mixture was added
  4. stirringThe mixture was stirred for an additional 16 hr at 80° C
  5. temperatureto cool to rt
  6. customInsoluble materials were removed by filtration through a celite pad
  7. customthe aqueous phase was separated from the filtrate
  8. extractionThe aqueous phase was extracted with EtOAc (50 mL)
  9. dry with materialThe combined organic phases were dried over anhydrous MgSO4
  10. customInsoluble materials were removed by filtration
  11. concentrationthe filtrate was concentrated under reduced pressure
  12. customThe residue was purified by HPLC (FA)

Sources & evidence

ORD record
ord-523619b599b84fec8565f3680775040b
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

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