Ethyl Acetate → 2-(4-Chloro-phenyl)-1-(1-cyclohexyl-2-cyclohexylmethoxy-ethyl)-5,6-difluoro-1H-benzoimidazole

HRID 417058

Reaktionsgleichung

Reaktionsgleichung von HRID 417058
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH:13]([CH:16]3[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]3)[CH2:14][OH:15])[C:11]3[CH:22]=[C:23]([F:27])[C:24]([F:26])=[CH:25][C:10]=3[N:9]=2)=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:31][CH:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1.C(OCC)(=O)C>CN(C)C=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH:13]([CH:16]3[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]3)[CH2:14][O:15][CH2:31][CH:32]3[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]3)[C:11]3[CH:22]=[C:23]([F:27])[C:24]([F:26])=[CH:25][C:10]=3[N:9]=2)=[CH:4][CH:3]=1

Komponenten

6

Edukt 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydride3×HCID 137636Cyclohexane, (bromomethyl)-3×HCID 666193102-[2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-ethanol

Produkt 1

HCID 666192022-(4-Chloro-phenyl)-1-(1-cyclohexyl-2-cyclohexylmethoxy-ethyl)-5,6-difluoro-1H-benzoimidazoleAusbeute 39 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of 0.58 g (1.48 mmol) 2-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-ethanol (Ex. 1, int. c) in 6 mL N,N-dimethylformamide, 71 mg (1.5 mmol, 55% dispersion in mineral oil) sodium hydride and after 5 min. 0.32 g (1.78 mmol) bromomethylcyclohexane were added. The reaction mixture was warmed to 50° C. and after 4 h another 71 mg sodium hydride and 0.32 g (1.78 mmol) bromomethylcyclohexane were added. A third batch sodium hydride and bromomethylcyclohexane were added after 3 h. After stirring overnight the reaction mixture was poured on water and ethyl acetate, extracted, the aqueous phase extracted twice with ethyl acetate and the aqueous phase extracted twice with ethyl acetate. The combined organic layers were washed twice with water and once with brine, dried over magnesium sulfate and evaporated. The crude product was purified by silica gel column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:ethylacetate (1:0 to 4:1) to yield the title compound as a white solid (39%). MS (Turbo Spray): m/z=487.3 [M+H].

Aufarbeitung

  1. additionwere added
  2. extractionextracted
  3. extractionthe aqueous phase extracted twice with ethyl acetate
  4. extractionthe aqueous phase extracted twice with ethyl acetate
  5. washThe combined organic layers were washed twice with water and once with brine
  6. dry with materialdried over magnesium sulfate
  7. customevaporated
  8. customThe crude product was purified by silica gel column chromatography
  9. washeluting with a gradient of n-heptane:ethylacetate (1:0 to 4:1)

Quellen und Nachweise

ORD-Eintrag
ord-367ccf9597e24e69ad6d210cb501c96b
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08088930B2

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