4-Pentyn-2-ol → HCID 67483913, compound

HRID 1936243Notes

Reaction equation

HRID 1936243 reaction equation
[CH3:1][O:2][C:3](=[O:18])[CH:4]([C:11]1[CH:16]=[CH:15][C:14](I)=[CH:13][CH:12]=1)[CH2:5][CH:6]1[CH2:10][CH2:9][CH2:8][CH2:7]1.[CH3:19][CH:20]([OH:24])[CH2:21][C:22]#[CH:23]>CN(C)C=O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.C(N(CC)CC)C.[I-]>[CH3:1][O:2][C:3](=[O:18])[CH:4]([C:11]1[CH:16]=[CH:15][C:14]([C:23]#[C:22][CH2:21][CH:20]([OH:24])[CH3:19])=[CH:13][CH:12]=1)[CH2:5][CH:6]1[CH2:10][CH2:9][CH2:8][CH2:7]1

Participants

7

Reactant 2

HCID 929154-Pentyn-2-olHCID 674834473-Cyclopentyl-2-(4-iodo-phenyl)-propionic acid methyl ester

Product 1

HCID 67483913HCID 67483913, compoundYield 92%

Reagents, catalysts & solvents 4

HCID 8471TriethylamineCatalystHCID 30165Iodide IonCatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A solution of 3-cyclopentyl-2-(4-iodo-phenyl)-propionic acid methyl ester (716 mg, 2.0 mmol) and triethylamine (2 mL, 0.01 mmol) in N,N-dimethylformamide (2 mL) was treated with 4-pentyne-2-ol (0.47 mL, 5.0 mmol). The resulting reaction mixture was degassed with argon and then treated with cooper iodide (10 mg, 0.05 mmol) and bis(triphenylphosphine)palladium (II) chloride (15 mg, 0.02 mmol). The reaction was then heated at 70° C. for 24 h. At this time, the reaction was cooled to 25° C. and concentrated in vacuo. The residue was diluted with ethyl acetate (40 mL) and a half-saturated aqueous sodium chloride solution (1×20 mL). The aqueous layer was back extracted with ethyl acetate (1×40 mL). The combined organic extracts were washed with a half-saturated aqueous sodium chloride solution (1×20 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 60/40 ethyl acetate/hexanes) afforded 3-cyclopentyl-2-[4-(4-hydroxy-pent-1-ynyl)-phenyl]-propionic acid methyl ester (578 mg, 92%) as an amber oil: EI-HRMS m/e calcd for C20H26O3 (M+) 314.1881, found 314.1888.

Workup

  1. customThe resulting reaction mixture
  2. customwas degassed with argon
  3. temperatureAt this time, the reaction was cooled to 25° C.
  4. concentrationconcentrated in vacuo
  5. additionThe residue was diluted with ethyl acetate (40 mL)
  6. extractionThe aqueous layer was back extracted with ethyl acetate (1×40 mL)
  7. washThe combined organic extracts were washed with a half-saturated aqueous sodium chloride solution (1×20 mL)
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-60915239b2f14f60902f595d893251d2
Source dataset
uspto-grants-2002_05
Patent number
US06388071B2

Reaction notes

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