Chlorotrimethylsilane → 3-chloro-2-methoxy-6-[(1E)-3-[4-(methylsulfonyl)phenyl]-1-(tetrahydro-2H-pyran-4-yl)prop-1-en-2-yl]pyridine

HRID 70612

Reaktionsgleichung

Reaktionsgleichung von HRID 70612
Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([CH3:12])(=[O:11])=[O:10])=[CH:5][CH:4]=1.C[Si](Cl)(C)C.BrCCBr.O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1.Br/[C:39](/[C:47]1[N:52]=[C:51]([O:53][CH3:54])[C:50]([Cl:55])=[CH:49][CH:48]=1)=[CH:40]\[CH:41]1[CH2:46][CH2:45][O:44][CH2:43][CH2:42]1>O1CCCC1.[Zn].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].O>[Cl:55][C:50]1[C:51]([O:53][CH3:54])=[N:52][C:47](/[C:39](/[CH2:2][C:3]2[CH:8]=[CH:7][C:6]([S:9]([CH3:12])(=[O:11])=[O:10])=[CH:5][CH:4]=2)=[CH:40]/[CH:41]2[CH2:42][CH2:43][O:44][CH2:45][CH2:46]2)=[CH:48][CH:49]=1

Komponenten

10

Edukt 5

HCID 6397ChlorotrimethylsilaneHCID 78391,2-DibromoethaneHCID 521585Tris(furan-2-yl)phosphaneHCID 27335814-(Methylsulfonyl)benzyl BromideHCID 584525136-[(Z)-1-bromo-2-(tetrahydro-2H-pyran-4-yl)ethenyl]-3-chloro-2-methoxypyridine

Produkt 1

HCID 673980903-chloro-2-methoxy-6-[(1E)-3-[4-(methylsulfonyl)phenyl]-1-(tetrahydro-2H-pyran-4-yl)prop-1-en-2-yl]pyridineAusbeute 59 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 23994ZincKatalysatorHCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

1-(Bromomethyl)-4-(methylsulfonyl)benzene (110 mg), trimethylsilyl chloride (12.5 μL) and 1,2-dibromoethane (8.6 μL) were added to a solution of zinc powder (78 mg) in tetrahydrofuran (4 mL) in the presence of an argon gas, and the mixture was stirred at 80° C. for two hours. The reaction solution was returned to room temperature. A solution of tris(dibenzylideneacetone)dipalladium (45 mg), tri(2-furyl)phosphine (69 mg) and 6-[(Z)-1-bromo-2-(tetrahydro-2H-pyran-4-yl)ethenyl]-3-chloro-2-methoxypyridine (380 mg) in tetrahydrofuran (2 mL) was added and the mixture was stirred at 90° C. for two hours. The reaction solution was poured into water, followed by extraction with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and filtered. The solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1→0:1) to give 3-chloro-2-methoxy-6-[(1E)-3-[4-(methylsulfonyl)phenyl]-1-(tetrahydro-2H-pyran-4-yl)prop-1-en-2-yl]pyridine as a yellow oil (110 mg).

Aufarbeitung

  1. customwas returned to room temperature
  2. stirringthe mixture was stirred at 90° C. for two hours
  3. extractionfollowed by extraction with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. customThe solvent was then evaporated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1→0:1)

Quellen und Nachweise

ORD-Eintrag
ord-8416f17639ed4d268133cfb7d52e8403
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08822503B2

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