Bromide ion → [(S)-1-(4-Chloro-3-methyl-phenyl)-2,2,2-trifluoro-ethyl]-(3-[1,3]dioxolan-2-yl-4-methyl-phenyl)-amine

HRID 1629724Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1629724
Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([C@H:9]([NH2:14])[C:10]([F:13])([F:12])[F:11])=[CH:5][C:4]=1[CH3:15].[Br-].Br[C:18]1[CH:19]=[CH:20][C:21]([CH3:29])=[C:22]([CH:24]2[O:28][CH2:27][CH2:26][O:25]2)[CH:23]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C([O-])([O-])=O.[Cs+].[Cs+]>CCOC(C)=O.C1(C)C=CC=CC=1.C(O)(C)(C)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([C@H:9]([NH:14][C:18]2[CH:19]=[CH:20][C:21]([CH3:29])=[C:22]([CH:24]3[O:25][CH2:26][CH2:27][O:28]3)[CH:23]=2)[C:10]([F:12])([F:13])[F:11])=[CH:5][C:4]=1[CH3:15]

Komponenten

10

Edukt 5

HCID 259Bromide ionHCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 57517340(S)-1-(4-chloro-3-methyl-phenyl)-2,2,2-trifluoro-ethylamine hydrochlorideHCID 583744502-(5-Bromo-2-methylphenyl)-1,3-dioxolane

Produkt 1

HCID 68258686[(S)-1-(4-Chloro-3-methyl-phenyl)-2,2,2-trifluoro-ethyl]-(3-[1,3]dioxolan-2-yl-4-methyl-phenyl)-amine

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 167845palladium(II) acetateKatalysatorHCID 1140TolueneLösungsmittelHCID 6386tert-ButanolLösungsmittelHCID 8857Ethyl AcetateLösungsmittel2×

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

(S)-1-(4-Chloro-3-methyl-phenyl)-2,2,2-trifluoro-ethylamine hydrochloride (5.00 g, 19.22 mmol) was taken up in EtOAc and washed with saturated aqueous NaHCO3, water (3×) and brine (2×). The organic layer was dried over MgSO4, filtered and concentrated. To a solution of the residue and bromide INT 31 (6.08 g, 24.99 mmol) in toluene (83 mL) and tert-butanol (33 mL) was added XPhos (1.83 g, 3.84 mmol) followed by Cs2CO3 (18.79 g, 57.67 mmol). The mixture was degassed for 10 minutes and Pd(OAc)2 (0.43 g, 1.92 mmol) was added. The reaction mixture was stirred at 100° C. for 4 hours. The mixture was diluted with EtOAc and washed with H2O (3×). The aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine (2×), dried over MgSO4, filtered and concentrated. The residue was purified by chromatography on silica gel (heptane/EtOAc) to afford INT 32.

Aufarbeitung

  1. washwashed with saturated aqueous NaHCO3, water (3×) and brine (2×)
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe mixture was degassed for 10 minutes
  6. washwashed with H2O (3×)
  7. extractionThe aqueous layer was extracted with EtOAc
  8. washThe combined organic layers were washed with brine (2×)
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe residue was purified by chromatography on silica gel (heptane/EtOAc)
  13. customto afford INT 32

Quellen und Nachweise

ORD-Eintrag
ord-74a3ba2666124bf99eca54a2ebb33ed4
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08791100B2

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