Cesium carbonate → 2-Bromo-6-(7,7-difluoro-1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-4-fluorobenzyl Acetate

HRID 519332

Reaktionsgleichung

Reaktionsgleichung von HRID 519332
[F:1][C:2]1([F:16])[CH2:10][C:9]2[N:8]3[CH2:11][CH2:12][NH:13][C:14](=[O:15])[C:7]3=[CH:6][C:5]=2[CH2:4][CH2:3]1.[C:17]([O:20][CH2:21][C:22]1[C:27]([Br:28])=[CH:26][C:25]([F:29])=[CH:24][C:23]=1Br)(=[O:19])[CH3:18].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[C:17]([O:20][CH2:21][C:22]1[C:23]([N:13]2[CH2:12][CH2:11][N:8]3[C:9]4[CH2:10][C:2]([F:1])([F:16])[CH2:3][CH2:4][C:5]=4[CH:6]=[C:7]3[C:14]2=[O:15])=[CH:24][C:25]([F:29])=[CH:26][C:27]=1[Br:28])(=[O:19])[CH3:18]

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 670165932,6-Dibromo-4-fluorobenzyl acetateHCID 86683735HCID 86683735, Verbindung

Produkt 1

HCID 866837362-Bromo-6-(7,7-difluoro-1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-4-fluorobenzyl AcetateAusbeute 62 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A 100-mL round-bottomed flask equipped with a reflux condenser was charged with 1,4-dioxane (40 mL), 113o (890 mg, 3.94 mmol), 2,6-dibromo-4-fluorobenzyl acetate 101c (3847 mg, 11.8 mmol), Pd2(dba)3 (180 mg, 0.197 mmol), XantPhos (227 mg, 0.394 mmol), and cesium carbonate (2.57 g, 7.88 mmol). After three cycles of vacuum/argon flush, the mixture was heated at 100° C. for 16 h. It was then filtered and the filtrate was evaporated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 3:1 petroleum ether/ethyl acetate to afford 113p (1100 mg, 62%) as a white solid. MS-ESI: [M+H]+ 471.1.

Aufarbeitung

  1. customA 100-mL round-bottomed flask equipped with a reflux condenser
  2. customAfter three cycles of vacuum/argon flush
  3. filtrationIt was then filtered
  4. customthe filtrate was evaporated under reduced pressure
  5. customThe residue was purified by silica-gel column chromatography
  6. washeluting with 3:1 petroleum ether/ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-67e7368b209f4a1ba7c483220f7fd5d1
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09115152B2

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