2,4,6-Trimethylpyridine → HCID 56970896, compound

HRID 1615479Notes

Reaction equation

HRID 1615479 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:13]3[CH:14]=[C:15]([C:17]4[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=4)[S:16][C:12]=3[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.CC1C=C(C)N=C(C)C=1.S(OOS([O-])(=O)=O)([O-])(=O)=[O:33].[K+].[K+]>C(#N)C.O1CCOCC1.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Cu+2]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:13]3[CH:14]=[C:15]([C:17]4[CH:18]=[CH:19][N:20]=[CH:21][CH:22]=4)[S:16][C:12]=3[C:11](=[O:33])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1

Participants

8

Reactant 3

HCID 79532,4,6-TrimethylpyridineHCID 24412Potassium PersulfateHCID 68183338HCID 68183338, compound

Product 1

HCID 56970896HCID 56970896, compoundYield 66.3%

Reagents, catalysts & solvents 4

HCID 24463Copper sulfate pentahydrateCatalystHCID 962WaterSolvent2×HCID 6342AcetonitrileSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

In a 100 mL round bottomed flask was placed 4-[4-(4-chlorophenyl)-4,5,6,7-tetrahydro-1-benzothien-2-yl]pyridine (821 mg, 2.52 mmol) and then dissolved in acetonitrile (10 mL) and 1,4-dioxane (10 mL). Then γ-Collidine (1.5 mL, 11 mmol) was added. To the mixture were added freshly prepared suspension of potassium persulfate (2.96 g, 10.9 mmol) and Copper(II) sulfate pentahydrate (278 mg, 1.11 mmol) in water (20 mL). The resulting mixture was stirred 6 h at 80° C. After stirring was continued for additional 1.5 h at the same temperature no increase in product formation was observed. The mixture was allowed to cool to rt and then was diluted with water (50 mL) and then extracted with EtOAc (50 mL×2). The combined organic phase was washed with freshly prepared 10% aqueous NaHSO3 (50 mL), saturated aqueous solution of NaHCO3 (50 mL), brine (50 mL), dried over anhydrous MgSO4. Insoluble materials were removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by pre-packed silica gel (24 g) column chromatography eluted with a 30% to 100% EtOAc/hexane to yield title compound (568 mg; 66.3%) as a colorless crystalline solid.

Workup

  1. customIn a 100 mL round bottomed flask was placed
  2. additionTo the mixture were added freshly prepared
  3. stirringAfter stirring
  4. waitwas continued for additional 1.5 h at the same temperature
  5. temperatureno increase in product formation
  6. temperatureto cool to rt
  7. extractionextracted with EtOAc (50 mL×2)
  8. washThe combined organic phase was washed with freshly prepared 10% aqueous NaHSO3 (50 mL), saturated aqueous solution of NaHCO3 (50 mL), brine (50 mL)
  9. dry with materialdried over anhydrous MgSO4
  10. customInsoluble materials were removed by filtration
  11. concentrationthe filtrate was concentrated under reduced pressure
  12. customThe residue was purified by pre-packed silica gel (24 g) column chromatography
  13. washeluted with a 30% to 100% EtOAc/hexane

Sources & evidence

ORD record
ord-eb7af8e839ff4deb82eaa53e1d887d36
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

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