Benzyl mercaptan → HCID 86687462, Verbindung

HRID 1473414

Reaktionsgleichung

Reaktionsgleichung von HRID 1473414
Br[C:2]1[CH:11]=[C:10]2[C:5]([C:6](Cl)=[C:7]([N+:12]([O-:14])=[O:13])[CH:8]=[N:9]2)=[CH:4][CH:3]=1.[CH3:16][O:17][C:18]1[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[CH:20][C:19]=1B(O)O.C(=O)([O-])[O-].[K+].[K+].CCN(C(C)C)C(C)C.[CH2:46]([SH:53])[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1>CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].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].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>[CH2:46]([S:53][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([C:19]3[CH:20]=[CH:21][C:22]([C:24]([F:27])([F:26])[F:25])=[CH:23][C:18]=3[O:17][CH3:16])=[C:7]([N+:12]([O-:14])=[O:13])[CH:8]=[N:9]2)=[CH:4][CH:3]=1)[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1

Komponenten

10

Edukt 5

HCID 7509Benzyl mercaptanHCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 219843617-Bromo-4-chloro-3-nitroquinolineHCID 24901776(2-Methoxy-4-(trifluoromethyl)phenyl)boronic acid

Produkt 1

HCID 86687462HCID 86687462, VerbindungAusbeute 83 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)KatalysatorHCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

A round-bottom flask was charged with 7-bromo-4-chloro-3-nitroquinoline (1.083 g, 3.77 mmol, from Capot Chemical, Zhejiang, China), (2-methoxy-4-(trifluoromethyl)phenyl)boronic acid (0.911 g, 4.14 mmol), potassium carbonate (1.562 g, 11.30 mmol), and PdCl2(dppf) (0.138 g, 0.188 mmol). The flask was flushed with Ar (g), then 1,4-dioxane (9.42 ml) and water (3.14 ml) were added. The flask was fitted with a reflux condenser and lowered into a 60° C. oil bath for 45 min. The mixture was diluted with water and extracted with EtOAc (2×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was taken up in 1,4-dioxane (9.42 ml). Xantphos (0.109 g, 0.188 mmol), Pd2(dba)3 (0.086 g, 0.094 mmol), n,n-diisopropylethylamine (1.316 ml, 7.53 mmol), and benzyl mercaptan (0.490 ml, 4.14 mmol) were added in sequence. The reflux condenser was attached, and the flask was heated to 60° C. for 2 h. The mixture was cooled to room temperature, diluted with EtOAc, then filtered through diatomaceous earth. The filtrate was concentrated, and the residue was purified by chromatography on silica gel (40-g column, 25-g silica gel loading column, 0 to 40% EtOAc/Heptane) to give 7-(benzylthio)-4-(2-methoxy-4-(trifluoromethyl)phenyl)-3-nitroquinoline (1.4698 g, 3.12 mmol, 83% yield) as a yellow solid. NMR indicated a 70:30 mixture of desired product to bis-coupling byproduct form the first step. m/z (ESI) 471.2 (M+H)+.

Aufarbeitung

  1. customThe flask was flushed with Ar (g)
  2. addition1,4-dioxane (9.42 ml) and water (3.14 ml) were added
  3. customThe flask was fitted with a reflux condenser
  4. customlowered into a 60° C.
  5. customfor 45 min
  6. additionThe mixture was diluted with water
  7. extractionextracted with EtOAc (2×)
  8. dry with materialThe combined organic extracts were dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. temperatureThe mixture was cooled to room temperature
  12. filtrationfiltered through diatomaceous earth
  13. concentrationThe filtrate was concentrated
  14. customthe residue was purified by chromatography on silica gel (40-g column, 25-g silica gel loading column, 0 to 40% EtOAc/Heptane)

Quellen und Nachweise

ORD-Eintrag
ord-1763428fba6f44d8b8d0352da00441da
Quelldatensatz
uspto-grants-2015_04
Patentnummer
US09012443B2

Verknüpfte Notizen

Wird geladen…