2-Methyl-3-butyn-2-ol → HCID 9898935, compound

HRID 2374177Notes

Reaction equation

HRID 2374177 reaction equation
Br[C:2]1[S:3][CH:4]=[CH:5][N:6]=1.C(N(CC)CC)C.[CH3:14][C:15]([OH:19])([C:17]#[CH:18])[CH3:16]>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>[S:3]1[CH:4]=[CH:5][N:6]=[C:2]1[C:18]#[C:17][C:15]([CH3:16])([OH:19])[CH3:14]

Participants

7

Reactant 3

HCID 82582-Methyl-3-butyn-2-olHCID 8471TriethylamineHCID 764302-Bromothiazole

Product 1

HCID 9898935HCID 9898935, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

2-Bromo-1,3-thiazole (6.0 g, 37 mmol) and CuI (1.3 g, 7.3 mmol) were combined in DME (150 mL) and argon gas was bubbled through the suspension for several minutes to deoxygenate the mixture. Triethylamine (25 mL, 180 mmol) and PdCl2(PPh3)2 (2.5 g, 3.7 mmol) were added and 2-methyl-3-butyne-2-ol (4.6 g, 55 mmol) was added dropwise. After stirring at ambient temperature for 16 h, GC/MS showed the reaction was not complete. The reaction was heated to reflux for 2 h. The mixture was filtered through Celite.™., the filter pad was washed thoroughly with ethyl acetate, and the combined filtrates were concentrated in vacuo. The residue was dissolved in ethyl acetate (600 mL), washed with water (600 mL), brine (600 mL), dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography eluting with hexane then 7:3 hexane:ethyl acetate to afford 4-(2-thiazolyl)-2-methyl-3-butyn-2-ol contaminated with 2,7-dimethyl-but-3,5-diyne-2,7-diol. (The dimer of 2-methyl-3-butyne-2-ol) The product was crystallized from boiling hexane to afford 2-methyl-4-(1,3-thiazol-2-yl)-3-butyn-2-ol (2.18 g, 36% yield) as off white crystals that were contaminated with a small amount of 2,7-dimethyl-but-3,5-diyne-2,7-diol. M.p. 69-70° C. 1H NMR (CDCl3, 300 MHz) Δ7.80 (d, J=3.0 Hz, 1H), 7.34 (d, J=3.0 Hz, 1H), 4.40 (s, 1H), 1.65 (s, 6H). MS (ESI) 168.1 (M++H).

Workup

  1. customargon gas was bubbled through the suspension for several minutes
  2. customto deoxygenate the mixture
  3. temperatureThe reaction was heated
  4. temperatureto reflux for 2 h
  5. filtrationThe mixture was filtered through Celite
  6. wash, the filter pad was washed thoroughly with ethyl acetate
  7. concentrationthe combined filtrates were concentrated in vacuo
  8. dissolutionThe residue was dissolved in ethyl acetate (600 mL)
  9. washwashed with water (600 mL), brine (600 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-5ee508c47bd44ff389b648225e0c0e51
Source dataset
uspto-grants-2008_12
Patent number
US07462619B2

Reaction notes

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