Propargyl alcohol → HCID 19261444, compound

HRID 1432872Notes

Reaction equation

HRID 1432872 reaction equation
Br[C:2]1[S:6][C:5]([Cl:7])=[CH:4][CH:3]=1.[CH2:8]([OH:11])[C:9]#[CH:10]>N1CCCCC1.CCOC(C)=O.CCOCC.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cu]I>[Cl:7][C:5]1[S:6][C:2]([C:10]#[C:9][CH2:8][OH:11])=[CH:3][CH:4]=1

Participants

7

Reactant 2

HCID 7859Propargyl alcoholHCID 761332-Bromo-5-chlorothiophene

Product 1

HCID 19261444HCID 19261444, compoundYield 9.1%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8082PiperidineSolventHCID 21584169Diethylether ethylacetateSolvent

Conditions

Temperature
80 °C

Procedure

Nitrogen (g) is bubbled through a solution of 5-bromo-2-chloro-thiophene (1.00 g, 5.06 mmol) in 8 mL of piperidine. After 5 min, propargyl alcohol (0.32 mL, 5.56 mmol), tetrakis(triphenylphosphine) palladium(0) (0.06 g) and CuI (catalytic amount) are added to the solution. The mixture is heated at 80° C. for 1 h in a sealed glass vessel. At this time, the mixture is cooled and diluted with EtOAc/Et2O. The organic layer is washed 3N HCl, water, saturated NaHCO3 solution and saturated NaCl solution. The organic layer is dried, filtered and concentrated. The crude residue is purified via flash column chromatography eluting with a gradient of 10% EtOAc/hexanes to 20% EtOAc/hexanes to give the title compound (0.8 g, 0.46 mmol) as an oil. 1H NMR (DMSO-d6, 300 MHz) δ6.99 (d, 1H), 6.80 (d, 1H), 4.49 (s, 2H), 1.90 (bs, 1H). EI MS, [M]+=172, 174 (Cl pattern).

Workup

  1. temperatureAt this time, the mixture is cooled
  2. washThe organic layer is washed 3N HCl, water, saturated NaHCO3 solution and saturated NaCl solution
  3. customThe organic layer is dried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude residue is purified via flash column chromatography
  7. washeluting with a gradient of 10% EtOAc/hexanes to 20% EtOAc/hexanes

Sources & evidence

ORD record
ord-4829438a7da24af9b7034f1e1f6884f1
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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