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

HRID 1936238노트

반응식

HRID 1936238 반응식
[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

참가 물질

7

반응물 2

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

생성물 1

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

시약·촉매·용매 4

HCID 8471Triethylamine촉매HCID 30165Iodide Ion촉매HCID 6102075Dichlorobis(triphenylphosphine)palladium촉매HCID 6228Dimethylformamide용매

반응 조건

온도
70 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-6996b5b620e645c8ba6a80ab63d04a44
출처 데이터셋
uspto-grants-2002_05
특허 번호
US06388071B2

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