3-Methyl-1-pentyn-3-ol → 3-Cyclopentyl-2-[4-(3-hydroxy-3-methyl-pent-1-ynyl)-phenyl]-propionic acid methyl ester

HRID 1936238Notes

Reaction equation

HRID 1936238 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][C:20]([OH:25])([CH2:23][CH3:24])[C:21]#[CH:22]>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:22]#[C:21][C:20]([OH:25])([CH3:19])[CH2:23][CH3:24])=[CH:13][CH:12]=1)[CH2:5][CH:6]1[CH2:10][CH2:9][CH2:8][CH2:7]1

Participants

7

Reactant 2

HCID 64943-Methyl-1-pentyn-3-olHCID 674834473-Cyclopentyl-2-(4-iodo-phenyl)-propionic acid methyl ester

Product 1

HCID 674841063-Cyclopentyl-2-[4-(3-hydroxy-3-methyl-pent-1-ynyl)-phenyl]-propionic acid methyl esterYield 102.5%

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 3-methyl-1-pentyn-3-ol (0.56 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-(3-hydroxy-3-methyl-pent-1-ynyl)-phenyl]-propionic acid methyl ester (673 mg, 98%) as an orange oil: EI-HRMS m/e calcd for C21H28O3 (M+) 328.2038, found 328.2040.

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-6996b5b620e645c8ba6a80ab63d04a44
Source dataset
uspto-grants-2002_05
Patent number
US06388071B2

Reaction notes

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