Hexane → 2-(3-Cyclohexyl-1-propynyl)-1,3-thiazole

HRID 902065Notes

Reaction equation

HRID 902065 reaction equation
Br[C:2]1[S:3][CH:4]=[CH:5][N:6]=1.C(N(CC)CC)C.[CH:14]1([CH2:20][C:21]#[CH:22])[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]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>[CH:14]1([CH2:20][C:21]#[C:22][C:2]2[S:3][CH:4]=[CH:5][N:6]=2)[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1

Participants

9

Reactant 4

HCID 8058HexaneHCID 8471TriethylamineHCID 764302-BromothiazoleHCID 87265(Prop-2-yn-1-yl)cyclohexane

Product 1

HCID 98558042-(3-Cyclohexyl-1-propynyl)-1,3-thiazoleYield 46.3%

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, 12 mmol) and CuI (185 mg, 0.97 mmol) were combined in DME (30 mL) and argon gas was bubbled through the suspension for several minutes to deoxygenate the mixture. Triethylamine (8.5 mL, 61 mmol) and PdCl2(PPh3)2 (340 mg, 0.49 mmol) were added and 3-cyclohexyl-1-propyne (2.9 g, 24 mmol) was added dropwise. The reaction was stirred at ambient temperature for 16 h at which time GC/MS analysis indicated that 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 (300 mL), washed with water (300 mL), brine (300 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-(3-cyclohexyl-1-propynyl)-1,3-thiazole (1.14 g, 46% yield) as a yellow oil. 1H NMR (CDCl3, 300 MHz) Δ7.76 (d, J=3.0 Hz, 1H), 7.27 (d, J=3.0 Hz, 1H), 2.35 (d, J=6 Hz, 2H), 1.89-1.61 (m, 5H), 1.3-1.03 (m, 6H). MS (ESI) 205.9 (M+H).

Workup

  1. customargon gas was bubbled through the suspension for several minutes
  2. customto deoxygenate the mixture
  3. filtrationThe mixture was filtered through Celite
  4. wash™, and the filter pad was washed thoroughly with ethyl acetate
  5. concentrationThe combined filtrates were concentrated in vacuo
  6. dissolutionThe residue was dissolved in ethyl acetate (300 mL)
  7. washwashed with water (300 mL), brine (300 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by column chromatography
  12. washeluting with hexane

Sources & evidence

ORD record
ord-7d141d563afd4282ac065c8cfddbec21
Source dataset
uspto-grants-2008_04
Patent number
US07365074B2

Reaction notes

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