N,N-Dimethylpropargylamine → 3-Cyclopentyl-2-[4-(3-dimethylamino-prop-1-ynyl)-phenyl]-propionic acid methyl ester

HRID 1936253Notes

Reaction equation

HRID 1936253 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][N:20]([CH3:24])[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][N:20]([CH3:24])[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 81643N,N-DimethylpropargylamineHCID 674834473-Cyclopentyl-2-(4-iodo-phenyl)-propionic acid methyl ester

Product 1

HCID 674848033-Cyclopentyl-2-[4-(3-dimethylamino-prop-1-ynyl)-phenyl]-propionic acid methyl esterYield 91.2%

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 1-dimethylamino-2-propyne (0.54 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 washed with a half-saturated aqueous sodium chloride solution (1×20 mL). The resulting aqueous layer was back extracted with ethyl acetate (1×120 mL). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 95/5 chloroform/methanol) afforded 3-cyclopentyl-2-[4-(3-dimethylamino-prop-1-ynyl)-phenyl]-propionic acid methyl ester (572 mg, 91%) as an amber oil: EI-HRMS m/e calcd for C20H27NO3 (M+) 313.2051, found 312.1850.

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. washwashed with a half-saturated aqueous sodium chloride solution (1×20 mL)
  7. extractionThe resulting aqueous layer was back extracted with ethyl acetate (1×120 mL)
  8. dry with materialThe combined organic extracts were dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e79224c62e4c48599877597bee4ae132
Source dataset
uspto-grants-2002_05
Patent number
US06388071B2

Reaction notes

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