Hexane → HCID 22291335, compound

HRID 967748Notes

Reaction equation

HRID 967748 reaction equation
Br[C:2]1[S:3][CH:4]=[CH:5][N:6]=1.C(N(CC)CC)C.[C:14]1([CH3:22])[CH:19]=[CH:18][CH:17]=[C:16]([C:20]#[CH:21])[CH:15]=1.CCCCCC>COCCOC.[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.C(OCC)(=O)C>[CH3:22][C:14]1[CH:15]=[C:16]([C:20]#[C:21][C:2]2[S:3][CH:4]=[CH:5][N:6]=2)[CH:17]=[CH:18][CH:19]=1

Participants

9

Reactant 4

HCID 8058HexaneHCID 8471TriethylamineHCID 764302-BromothiazoleHCID 1366003-Methylphenylacetylene

Product 1

HCID 22291335HCID 22291335, compoundYield 16.3%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-Bromo-1,3-thiazole (2.0 g, 13 mmol) and CuI (330 mg, 1.7 mmol) were combined in DME (25 mL) and argon gas was bubbled through the suspension for several minutes to deoxygenate the mixture. Triethylamine (5.7 mL, 43 mmol) and PdCl2(PPh3)2 (604 mg, 0.86 mmol) were added and m-tolylacetylene (1.0 g, 8.6 mmol) was added dropwise. The reaction mixture was heated under reflux for 4 h at which time GC/MS showed the reaction was complete. The mixture was filtered through Celite™, and the filter pad was washed thoroughly with ethyl acetate. The combined filtrates were concentrated in vacuo. The residue was dissolved in ethyl acetate (200 mL), washed with water (200 mL), brine (200 mL), dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography eluting with hexane then 98:2 hexane:ethyl acetate to afford 2-[2-(3-methylphenyl)ethynyl]-thiazole (280 mg, 16% yield) as a yellow oil which was still impure by 1H NMR analysis. The compound (280 mg) was dissolved in DMSO and purified by preparative HPLC with a 30 min gradient from 70:30 water:acetonitrile to 100% acetonitrile to afford pure 2-[(3-methylphenyl)ethynyl]-1,3-thiazole (122 mg, 6% yield) as a yellow oil. 1H NMR (CDCl3, 300 MHz) δ 7.84 (d, J=3.0 Hz, 1H), 7.40–7.34 (m, 3H), 7.28–7.18 (m, 2H), 2.34 (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. temperatureThe reaction mixture was heated
  4. temperatureunder reflux for 4 h at which time GC/MS
  5. filtrationThe mixture was filtered through Celite™
  6. washthe filter pad was washed thoroughly with ethyl acetate
  7. concentrationThe combined filtrates were concentrated in vacuo
  8. dissolutionThe residue was dissolved in ethyl acetate (200 mL)
  9. washwashed with water (200 mL), brine (200 mL)
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe residue was purified by column chromatography
  14. washeluting with hexane

Sources & evidence

ORD record
ord-2cc4e74938c7452ebf80e77b3c622e3a
Source dataset
uspto-grants-2005_10
Patent number
US06956049B1

Reaction notes

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