Potassium Fluoride → 1-[2-(4-Trifluoromethylphenyl)thiazol-5-yl]-2-(5-methylthien-2-yl)ethyne

HRID 2232392

Reaction equation

HRID 2232392 reaction equation
C[Si](C)(C)[C:3]#[C:4][C:5]1[S:6][C:7]([CH3:10])=[CH:8][CH:9]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[F-].[K+].[F:33][C:34]([F:48])([F:47])[C:35]1[CH:40]=[CH:39][C:38]([C:41]2[S:42][C:43](I)=[CH:44][N:45]=2)=[CH:37][CH:36]=1>C(#N)C.C(N(CC)CC)C.C(OCC)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[F:48][C:34]([F:33])([F:47])[C:35]1[CH:36]=[CH:37][C:38]([C:41]2[S:42][C:43]([C:3]#[C:4][C:5]3[S:6][C:7]([CH3:10])=[CH:8][CH:9]=3)=[CH:44][N:45]=2)=[CH:39][CH:40]=1

Participants

10

Reactant 4

HCID 522689Potassium FluorideHCID 2724141Tetrabutylammonium FluorideHCID 146019702-(4-Trifluoromethylphenyl)-5-iodothiazoleHCID 14643579(5-Methyl-2-thienylethynyl)trimethylsilane

Product 1

HCID 144053511-[2-(4-Trifluoromethylphenyl)thiazol-5-yl]-2-(5-methylthien-2-yl)ethyneYield 27.8%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 3283Diethyl EtherSolventHCID 6342AcetonitrileSolventHCID 8471TriethylamineSolvent

Procedure

Under a dry nitrogen atmosphere, a stirred mixture of 0.70 gram (0.0036 mole) of 1-trimethylsilyl-2-(5-methylthien-2-yl)ethyne, 0.11 gram (0.0040 mole) of tetrabutylammonium fluoride, and 0.24 gram (0.0041 mole) of potassium fluoride in 7 ml of acetonitrile and 20 ml of triethylamine was heated at reflux for one hour. To this mixture was added 1.0 gram (0.0033 mole) of 2-(4-trifluoromethylphenyl)-5-iodothiazole, 0.03 gram (4.0×10-4 mole) of dichlorobis(triphenylphosphine)palladium (II), and 0.02 gram (8.0×10-4 mole) of copper (I) iodide. This mixture was stirred at reflux for approximately 18 hours. The mixture was cooled and was diluted with diethyl ether. This mixture was washed in succession with an aqueous, saturated ammonium chloride solution, water, dilute hydrochloric acid, and an aqueous, saturated sodium chloride solution. The washed organic solution was dried over anhydrous magnesium sulfate and was filtered. The filtrate was evaporated under reduced pressure leaving a solid residue. This residue was purified by column chromatography on silica gel, eluting first with methylene chloride:hexane (50:50), then methylene chloride: hexane (50:40), and finally acetone:hexane (10:90), to yield 0.32 gram of 1-[2-(4-trifluoromethylphenyl)thiazol-5-yl]-2-(5-methylthien-2-yl)ethyne as a solid, m.p. 107°-108.5° C., Compound 33 of Table 1.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for one hour
  3. temperatureat reflux for approximately 18 hours
  4. temperatureThe mixture was cooled
  5. washThis mixture was washed in succession with an aqueous, saturated ammonium chloride solution, water, dilute hydrochloric acid
  6. dry with materialThe washed organic solution was dried over anhydrous magnesium sulfate
  7. filtrationwas filtered
  8. customThe filtrate was evaporated under reduced pressure
  9. customleaving a solid residue
  10. customThis residue was purified by column chromatography on silica gel
  11. washeluting first with methylene chloride:hexane (50:50)

Sources & evidence

ORD record
ord-be1b90bc8054443588bc3a572ec84704
Source dataset
uspto-grants-1988_11
Patent number
US04788207

Linked notes

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