Cesium carbonate → (3S)-3-hydroxy-1-[4-(trifluoromethyl)phenyl]pyrrolidin-2-one

HRID 514878Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 514878
[OH:1][C@H:2]1[CH2:6][CH2:5][NH:4][C:3]1=[O:7].Br[C:9]1[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][CH:10]=1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[OH:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:9]2[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][CH:10]=2)[C:3]1=[O:7]

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 67872Benzene, 1-bromo-4-(trifluoromethyl)-HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 11029774(3S)-3-hydroxypyrrolidin-2-one

Produkt 1

HCID 86700658(3S)-3-hydroxy-1-[4-(trifluoromethyl)phenyl]pyrrolidin-2-one

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a 1,4-dioxane (20 mL) solution of (3S)-3-hydroxypyrrolidin-2-one (372 mg, 3.68 mmol) and 1-bromo-4-(trifluoromethyl)benzene (508 μL, 3.68 mmol) at room temperature was added 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (64 mg, 0.11 mmol), palladium(II) acetate (17 mg, 0.070 mmol) and cesium carbonate (1.80 g, 5.52 mmol). After stirring at 80° C. for 16 hours, the reaction mixture was allowed to cool down to room temperature and partitioned between diethyl ether (100 mL) and brine (100 mL). The organic layer was washed with brine (2×100 mL), dried (magnesium sulfate) and concentrated in vacuo to afford the crude product. Chromatography over silica gel, eluting with hexanes/ethyl acetate, afforded the title compound. 1H NMR (500 MHz, CDCl3) δ 7.81 (d, J=8.6 Hz, 2H), 7.64 (d, J=8.7 Hz, 2H), 4.52-4.48 (m, 1H), 3.89-3.77 (m, 2H), 3.05 (br s, 1H), 2.68-2.62 (m, 1H), 2.18-2.09 (m, 1H).

Aufarbeitung

  1. temperatureto cool down to room temperature
  2. custompartitioned between diethyl ether (100 mL) and brine (100 mL)
  3. washThe organic layer was washed with brine (2×100 mL)
  4. dry with materialdried (magnesium sulfate)
  5. concentrationconcentrated in vacuo
  6. customto afford the crude product
  7. washChromatography over silica gel, eluting with hexanes/ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-0d0bee8ae832420a8df94b1192247e57
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09108920B2

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