4-Bromo-2-fluoro-1-iodobenzene → Rac-[2-(4-bromo-2-fluoro-phenyl)-1-(3,4-dichloro-phenyl)-2-oxo-ethyl]-carbamic acid tert-butyl ester

HRID 384893

Reaktionsgleichung

Reaktionsgleichung von HRID 384893
[Br:1][C:2]1[CH:7]=[CH:6][C:5](I)=[C:4]([F:9])[CH:3]=1.C([Li])CCC.[C:15]([O:19][C:20](=[O:37])[NH:21][CH:22]([C:29]1[CH:34]=[CH:33][C:32]([Cl:35])=[C:31]([Cl:36])[CH:30]=1)[C:23](=[O:28])N(OC)C)([CH3:18])([CH3:17])[CH3:16]>O1CCCC1>[C:15]([O:19][C:20](=[O:37])[NH:21][CH:22]([C:29]1[CH:34]=[CH:33][C:32]([Cl:35])=[C:31]([Cl:36])[CH:30]=1)[C:23]([C:5]1[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][C:4]=1[F:9])=[O:28])([CH3:18])([CH3:16])[CH3:17]

Komponenten

5

Edukt 3

HCID 27245164-Bromo-2-fluoro-1-iodobenzeneHCID 87442373Rac-[(3,4-dichloro-phenyl)-(methoxy-methyl-carbamoyl)-methyl]-carbamic acid tert-butyl ester2×HCID 178418339Butyllithium

Produkt 1

HCID 68409235Rac-[2-(4-bromo-2-fluoro-phenyl)-1-(3,4-dichloro-phenyl)-2-oxo-ethyl]-carbamic acid tert-butyl ester

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a stirred solution of 1.75 g (5.78 mmol) 1-bromo-3-fluoro-4-iodo-benzene in 12 ml dry tetrahydrofuran were added at −78° C. 3.61 ml (5.78 mmol) of a 1.6M butyl lithium solution in hexanes. After 1 h 0.600 g (1.65 mmol) rac-[(3,4-dichloro-phenyl)-(methoxy-methyl-carbamoyl)-methyl]-carbamic acid tert-butyl ester (Intermediate 9) were added and stirred at −78° C. fur further 4 h. Then the reaction mixture was quenched by addition of saturated aqueous ammonium chloride solution, warmed to ambient temperature and extracted with ethyl acetate. The combined extracts were washed with brine, dried over Na2SO4, filtered and evaporated. The crude product was purified by flash-chromatography over silica gel with a heptane/AcOEt gradient starting with pure heptane: rac-[2-(4-bromo-2-fluoro-phenyl)-1-(3,4-dichloro-phenyl)-2-oxo-ethyl]-carbamic acid tert-butyl ester was obtained as a colorless viscous oil: MS (ISP): 476.0 and 477.9 (M+H)+.

Aufarbeitung

  1. customThen the reaction mixture was quenched by addition of saturated aqueous ammonium chloride solution
  2. temperaturewarmed to ambient temperature
  3. extractionextracted with ethyl acetate
  4. washThe combined extracts were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude product was purified by flash-chromatography over silica gel with a heptane/AcOEt gradient

Quellen und Nachweise

ORD-Eintrag
ord-760c245c50a54948b3aed84b6886ac37
Quelldatensatz
uspto-grants-2013_02
Patentnummer
US08367838B2

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