Cesium carbonate → methyl 8-[(2R)-(1-(3-fluorophenyl)pyrrolidin-2-yl)]-2-morpholino-4-oxo-4H-chromene-6-carboxylate

HRID 41192

Reaktionsgleichung

Reaktionsgleichung von HRID 41192
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[O:8][C:9]3[C:14]([C:15](=[O:17])[CH:16]=2)=[CH:13][C:12]([C:18]([O:20][CH3:21])=[O:19])=[CH:11][C:10]=3[C@H:22]2[CH2:26][CH2:25][CH2:24][NH:23]2)[CH2:3][CH2:2]1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.Br[C:70]1[CH:75]=[CH:74][CH:73]=[C:72]([F:76])[CH:71]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C(O[Pd]OC(=O)C)(=O)C>[F:76][C:72]1[CH:71]=[C:70]([N:23]2[CH2:24][CH2:25][CH2:26][C@@H:22]2[C:10]2[CH:11]=[C:12]([C:18]([O:20][CH3:21])=[O:19])[CH:13]=[C:14]3[C:9]=2[O:8][C:7]([N:4]2[CH2:3][CH2:2][O:1][CH2:6][CH2:5]2)=[CH:16][C:15]3=[O:17])[CH:75]=[CH:74][CH:73]=1

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 140821-Bromo-3-fluorobenzeneHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86672411methyl 2-morpholino-4-oxo-8-[(2R)-pyrrolidin-2-yl]chromene-6-carboxylate

Produkt 1

HCID 86672418methyl 8-[(2R)-(1-(3-fluorophenyl)pyrrolidin-2-yl)]-2-morpholino-4-oxo-4H-chromene-6-carboxylateAusbeute 79 %

Reagenzien, Katalysatoren, Lösungsmittel 2

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

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

Diacetoxypalladium (3.3 mg, 0.01 mmol) was added to a stirred mixture of methyl 2-morpholino-4-oxo-8-[(2R)-pyrrolidin-2-yl]chromene-6-carboxylate (121 mg, 0.34 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (16.61 mg, 0.03 mmol), 1-bromo-3-fluorobenzene (0.047 mL, 0.42 mmol) and cesium carbonate (165 mg, 0.51 mmol) suspended in 1,4-dioxane (3.3 mL). The resulting suspension was degassed with argon and then stirred at 100° C. for 20 h. The reaction mixture was allowed to cool to room temperature, and the crude product was purified by flash chromatography on silica gel eluting with 0 to 7% propanol in DCM. The solvent was evaporated to dryness to afford methyl 8-[(2R)-(1-(3-fluorophenyl)pyrrolidin-2-yl)]-2-morpholino-4-oxo-4H-chromene-6-carboxylate (120 mg, 79%) as a yellow oil which solidified on standing. Mass Spectrum: m/z [M+H]+=453.

Aufarbeitung

  1. customThe resulting suspension was degassed with argon
  2. temperatureto cool to room temperature
  3. customthe crude product was purified by flash chromatography on silica gel eluting with 0 to 7% propanol in DCM
  4. customThe solvent was evaporated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-706017184de54f3e98b9bd3bfabb2fc4
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08530470B2

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