Acetone → (R)-2-{4-[4-(3-Ethoxymethyl-3,4-dihydro-1H-isoquinolin-2-ylmethyl)-3,5-diethyl-pyrazol-1-yl]-3,5-dimethylphenyl}-propan-2-ol

HRID 1740105Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1740105
C([Li])CCC.Br[C:7]1[CH:12]=[C:11]([CH3:13])[C:10]([N:14]2[C:18]([CH2:19][CH3:20])=[C:17]([CH2:21][N:22]3[C@@H:31]([CH2:32][O:33][CH2:34][CH3:35])[CH2:30][C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[CH2:23]3)[C:16]([CH2:36][CH3:37])=[N:15]2)=[C:9]([CH3:38])[CH:8]=1.[CH3:39][C:40]([CH3:42])=[O:41]>O1CCCC1>[CH2:34]([O:33][CH2:32][C@H:31]1[CH2:30][C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH2:23][N:22]1[CH2:21][C:17]1[C:16]([CH2:36][CH3:37])=[N:15][N:14]([C:10]2[C:11]([CH3:13])=[CH:12][C:7]([C:40]([OH:41])([CH3:42])[CH3:39])=[CH:8][C:9]=2[CH3:38])[C:18]=1[CH2:19][CH3:20])[CH3:35]

Komponenten

5

Edukt 3

HCID 180AcetoneHCID 53638919(R)-2-[1-(4-bromo-2,6-dimethylphenyl)-3,5-diethyl-1H-pyrazol-4-ylmethyl]-3-ethoxymethyl-1,2,3,4-tetrahydro-isoquinolineHCID 178418339Butyllithium

Produkt 1

HCID 53828411(R)-2-{4-[4-(3-Ethoxymethyl-3,4-dihydro-1H-isoquinolin-2-ylmethyl)-3,5-diethyl-pyrazol-1-yl]-3,5-dimethylphenyl}-propan-2-olAusbeute 70 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a solution of n-butyl lithium (2.5 M hexane solution; 0.16 ml, 0.39 mmol) chilled to -78° C., a solution of (R)-2-[1-(4-bromo-2,6-dimethylphenyl)-3,5-diethyl-1H-pyrazol-4-ylmethyl]-3-ethoxymethyl-1,2,3,4-tetrahydro-isoquinoline (180 mg, 0.35 mmol) in anhydrous tetrahydrofuran (1.0 ml) was added dropwise. After stirring at -78° C. for 10 minutes, anhydrous acetone (0.078 ml, 1.1 mmol) was added. The resulting mixture was warmed to ambient temperature, and stirred at that temperature for 1 hour. The reaction was quenched by addition of aqueous ammonium chloride (2 ml) and then extracted with ethyl acetate/water (5 ml of each). The separated organic extract was then extracted with an equal volume solution of aqueous ammonium chloride. The combined aqueous extracts were then extracted with a fresh equal-volume portion of ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate, and concentrated in vacuo to afford a yellow oil. Flash chromatography of the entire sample (silica gel, 40 micron mesh; elution with ethyl acetate/hexane=1:2 in volume) afforded the title compound (120 mg) as a faint yellow oil.

Aufarbeitung

  1. temperatureThe resulting mixture was warmed to ambient temperature
  2. stirringstirred at that temperature for 1 hour
  3. customThe reaction was quenched by addition of aqueous ammonium chloride (2 ml)
  4. extractionextracted with ethyl acetate/water (5 ml of each)
  5. extractionThe separated organic extract
  6. extractionwas then extracted with an equal volume solution of aqueous ammonium chloride
  7. extractionThe combined aqueous extracts were then extracted with a fresh equal-volume portion of ethyl acetate
  8. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  9. concentrationconcentrated in vacuo
  10. customto afford a yellow oil
  11. washFlash chromatography of the entire sample (silica gel, 40 micron mesh; elution with ethyl acetate/hexane=1:2 in volume)

Quellen und Nachweise

ORD-Eintrag
ord-4290cdbf963b489197963e7687b14aa0
Quelldatensatz
uspto-grants-1999_10
Patentnummer
US05968944

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