Acetonitrile → HCID 68183036, compound

HRID 1615545Notes

Reaction equation

HRID 1615545 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]2[C:14]3[CH:15]=[CH:16][S:17][C:13]=3[CH2:12][CH2:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].[O:18]1CCOCC1.C(#N)C.S(OOS([O-])(=O)=O)([O-])(=O)=O.[K+].[K+]>O.O.O.O.O.S([O-])([O-])(=O)=O.[Cu+2].O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]2[C:14]3[CH:15]=[CH:16][S:17][C:13]=3[C:12](=[O:18])[CH2:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 24412Potassium Persulfate2×HCID 312751,4-DioxaneHCID 68182902HCID 68182902, compound

Product 1

HCID 68183036HCID 68183036, compoundYield 38%

Reagents, catalysts & solvents 2

HCID 24463Copper sulfate pentahydrateCatalyst2×HCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

4-(3,4-Dichlorophenyl)-4,5,6,7-tetrahydro-1-benzothiophene (3.25 g, 11.5 mmol), 1,4-dioxane (93 mL), acetonitrile (93 mL), water (100 mL), copper(II) sulfate pentahydrate (11.46 g, 45.90 mmol), and potassium persulfate (12.41 g, 45.90 mmol) were combined in a round bottomed flask equipped with a stirbar. The mixture was stirred overnight at 90° C. under an atmosphere of nitrogen during which time the blue color of the reaction disappeared to leave a light brown solution with some light greenish solid. The reaction was cooled to rt then additional copper(II) sulfate pentahydrate (11.46 g, 45.90 mmol) and potassium persulfate (12.41 g, 45.91 mmol) were added and the reaction was stirred at 90° C. under an atmosphere of nitrogen for an additional 5 hours. The reaction was cooled to rt and quenched with a solution of saturated sodium bisulfite. Saturated NaHCO3 solution was added until the mixture was basic, then ethyl acetate was added, the biphasic mixture was transferred to a separatory funnel and the organic layer was separated. The aqueous layer was extracted with additional ethyl acetate. The organic layers were combined, dried over anhydrous sodium sulfate, filtered, and concentrated to leave crude product as darkish orange oil. The residue was purified using column chromatography on silica gel (330 g RediSep column, gradient 0% EA in hexane to 25% EA in hexane over 30 minutes) give the product 1.29 g (38% yield) product as a light tan solid. LCMS: (FA) ES+ 297, 299. 1H NMR (400 MHz, DMSO) δ 8.00-7.93 (d, J=5.0 Hz, 1H), 7.64-7.57 (d, J=8.3 Hz, 1H), 7.55-7.49 (d, J=2.1 Hz, 1H), 7.22-7.14 (dd, J=8.3, 2.1 Hz, 1H), 6.72-6.65 (d, J=5.0 Hz, 1H), 4.41-4.32 (dd, J=9.2, 4.8 Hz, 1H), 2.72-2.59 (m, 1H), 2.57-2.51 (m, 1H), 2.39-2.19 (m, 2H).

Workup

  1. customequipped with a stirbar
  2. customto leave a light brown solution with some light greenish solid
  3. temperatureThe reaction was cooled to rt
  4. stirringthe reaction was stirred at 90° C. under an atmosphere of nitrogen for an additional 5 hours
  5. temperatureThe reaction was cooled to rt
  6. customquenched with a solution of saturated sodium bisulfite
  7. additionSaturated NaHCO3 solution was added until the mixture
  8. additionethyl acetate was added
  9. customthe biphasic mixture was transferred to a separatory funnel
  10. customthe organic layer was separated
  11. extractionThe aqueous layer was extracted with additional ethyl acetate
  12. dry with materialdried over anhydrous sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customto leave crude product as darkish orange oil
  16. customThe residue was purified
  17. customon silica gel (330 g RediSep column, gradient 0% EA in hexane to 25% EA in hexane over 30 minutes)

Sources & evidence

ORD record
ord-6f15f2cd95284a0f8d8155dadec6fb33
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

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