Cesium carbonate → 7-Chloro-6-(3-phenylazetidin-1-yl)-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 1013117Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1013117
[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])[CH2:9][CH2:10][C:4]=2[C:3]=1OS(C(F)(F)F)(=O)=O.[C:27]1([CH:33]2[CH2:36][NH:35][CH2:34]2)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.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].C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])[CH2:9][CH2:10][C:4]=2[C:3]=1[N:35]1[CH2:36][CH:33]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:34]1

Komponenten

8

Edukt 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 289015863-PhenylazetidineHCID 574477477-Chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethylsulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Produkt 1

HCID 597990437-Chloro-6-(3-phenylazetidin-1-yl)-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepineAusbeute 35 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
95 °C

Versuchsvorschrift

Use 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (prepared essentially as described in Preparation 1) (183 mg, 0.43 mmol), 3-phenylazetidine (75.2 mg, 0.56 mmol), palladium (II) acetate) (9.0 mg, 0.04 mmol), tris(dibenzylideneacetone)dipalladium(0) (37 mg, 0.04 mmol), BINAP (racemic, 37 mg, 0.06 mmol), cesium carbonate (195 mg, 0.6 mmol), anhydrous toluene (10 mL) and degas and fill with nitrogen (3 times). Seal the system with septum and tighten it with copper wire when necessary. Heat the mixture at 95° C. for 8 h. Dilute with EtOAc, wash with saturated aqueous sodium bicarbonate solution, brine, dry (sodium sulfate), concentrate and purify (silica gel chromatography, eluting with 10:90 EtOAc:hexanes) to give the title compound (61 mg, 35%).

Aufarbeitung

  1. customdegas
  2. customSeal the system with septum
  3. additionDilute with EtOAc
  4. washwash with saturated aqueous sodium bicarbonate solution, brine
  5. dry with materialdry (sodium sulfate)
  6. concentrationconcentrate
  7. custompurify
  8. wash(silica gel chromatography, eluting with 10:90 EtOAc:hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-917e5fef252447158c401ba2de1ca585
Quelldatensatz
uspto-grants-2011_07
Patentnummer
US07981882B2

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