Diisopropylethylamine → (2S,4S)-1-[[N-[4-(2-tetrahydropyranyl)oxycarbonylbicyclo[2,2,2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile

HRID 227934Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 227934
[NH2:1][C:2]12[CH2:9][CH2:8][C:5]([C:10]([O:12][CH:13]3[CH2:18][CH2:17][CH2:16][CH2:15][O:14]3)=[O:11])([CH2:6][CH2:7]1)[CH2:4][CH2:3]2.C(N(C(C)C)CC)(C)C.Br[CH2:29][C:30]([N:32]1[CH2:36][C@@H:35]([F:37])[CH2:34][C@H:33]1[C:38]#[N:39])=[O:31]>C(#N)C>[O:14]1[CH2:15][CH2:16][CH2:17][CH2:18][CH:13]1[O:12][C:10]([C:5]12[CH2:6][CH2:7][C:2]([NH:1][CH2:29][C:30]([N:32]3[CH2:36][C@@H:35]([F:37])[CH2:34][C@H:33]3[C:38]#[N:39])=[O:31])([CH2:9][CH2:8]1)[CH2:3][CH2:4]2)=[O:11]

Komponenten

5

Edukt 3

HCID 81531DiisopropylethylamineHCID 21090395(2S,4S)-1-(2-bromoacetyl)-4-fluoropyrrolidine-2-carbonitrileHCID 231496982-Tetrahydropyranyl 4-aminobicyclo[2,2,2]octane-1-carboxylate

Produkt 1

HCID 59383132(2S,4S)-1-[[N-[4-(2-tetrahydropyranyl)oxycarbonylbicyclo[2,2,2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrileAusbeute 79,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel2×

Versuchsvorschrift

2-Tetrahydropyranyl 4-aminobicyclo[2.2.2]octane-1-carboxylate (62.9 mg) was suspended in acetonitrile (1 mL). To this solution, diisopropylethylamine (47 μL) was added and (2S,4S)-1-(2-bromoacetyl)-4-fluoropyrrolidine-2-carbonitrile (53.1 mg) in acetonitrile (0.8 mL) was added while the mixture was chilled in an ice bath. The mixture was stirred for 4 hours and concentrated. To the resulting residue, ethyl acetate and water were added, followed by an aqueous sodium bicarbonate solution to make the pH basic. The solution was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (eluant:dichloromethane:methanol=10:1) to give (2S,4S)-1-[[N-[4-(2-tetrahydropyranyl)oxycarbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (73.3 mg).

Aufarbeitung

  1. temperaturewas chilled in an ice bath
  2. concentrationconcentrated
  3. additionTo the resulting residue, ethyl acetate and water were added
  4. extractionThe solution was extracted with ethyl acetate
  5. washThe ethyl acetate layer was washed with saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue was purified by silica gel chromatography (eluant:dichloromethane:methanol=10:1)

Quellen und Nachweise

ORD-Eintrag
ord-3b341c4c65ca4cb691fc70ee2710081b
Quelldatensatz
uspto-grants-2009_07
Patentnummer
US07560569B2

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