Triethylamine → 4-Methyl-5-(phenylethynyl)-1,3-thiazole

HRID 967743Notes

Reaction equation

HRID 967743 reaction equation
Br[C:2]1[S:6][CH:5]=[N:4][C:3]=1[CH3:7].C(N(CC)CC)C.[C:15]1([C:21]#[CH:22])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>COCCOC.C(OCC)(=O)C.[Cu]I.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>[CH3:7][C:3]1[N:4]=[CH:5][S:6][C:2]=1[C:22]#[C:21][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 10821Phenylacetylene2×HCID 150209975-Bromo-4-methyl-1,3-thiazole

Product 1

HCID 222913364-Methyl-5-(phenylethynyl)-1,3-thiazoleYield 26%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 178418476HCID 178418476, compoundCatalyst2×HCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

5-Bromo-4-methyl-1,3-thiazole (570 mg, 3.2 mmol) and CuI (120 mg, 0.63 mmol) were combined in DME (5 mL) and argon gas was bubbled through the suspension for several minutes to deoxygenate the mixture. Triethylamine (2.0 mL, 14 mmol) and PdCl2(PPh3)2 (220 mg, 0.32 mmol) were added, followed by the dropwise addition of phenylacetylene (1.0 mL, 9.5 mmol). After 16 h stirring at ambient temperature additional phenylacetylene (0.35 mL, 3.2 mmol), CuI, (61 mg, 0.32 mmol), and PdCl2(PPh3)2 (110 mg, 0.16 mmol) were added and the reaction mixture was stirred for a further 16 h. The reaction was then heated to reflux, and after 3 h the reaction mixture was cooled, diluted with ethyl acetate (20 mL), and filtered through Celite™. The filter pad was washed thoroughly with ethyl acetate and the combined filtrates were washed with water (20 mL), brine (20 mL), dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with 95:5 hexane:ethyl acetate to afford 4-methyl-5-(phenylethynyl)-1,3-thiazole (166 mg, 26% yield) as a red oil. 1H NMR (CDCl3, 300 MHz) δ 8.62 (s, 1H), 7.54–7.50 (m, 2H), 7.37–7.26 (m, 3H), 2.6 (s, 3H). MS (ESI) 200.1 (M++H).

Workup

  1. customargon gas was bubbled through the suspension for several minutes
  2. customto deoxygenate the mixture
  3. additionwere added
  4. temperatureThe reaction was then heated
  5. temperatureto reflux
  6. temperatureafter 3 h the reaction mixture was cooled
  7. filtrationfiltered through Celite™
  8. washThe filter pad was washed thoroughly with ethyl acetate
  9. washthe combined filtrates were washed with water (20 mL), brine (20 mL)
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe residue was purified by column chromatography on silica gel eluting with 95:5 hexane

Sources & evidence

ORD record
ord-d965bd185b18457e94847cccf25491f7
Source dataset
uspto-grants-2005_10
Patent number
US06956049B1

Reaction notes

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