3,5-Dimethyl-4-hydroxybenzonitrile → 4-{2-[2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-ethoxy}-3,5-dimethyl-benzonitrile

HRID 417108Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 417108
[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.[CH3:28][C:29]1[CH:30]=[C:31]([CH:34]=[C:35]([CH3:38])[C:36]=1O)[C:32]#[N:33]>O1CCCC1>[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][C:36]3[C:35]([CH3:38])=[CH:34][C:31]([C:32]#[N:33])=[CH:30][C:29]=3[CH3:28])[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

4

Edukt 2

HCID 201763,5-Dimethyl-4-hydroxybenzonitrileHCID 666193102-[2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-ethanol

Produkt 1

HCID 666195034-{2-[2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-ethoxy}-3,5-dimethyl-benzonitrileAusbeute 22 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To an ice-cold solution of 0.38 g (0.97 mmol) 2-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-ethanol (Ex. 1, int. c), 0.157 g (1.07 mmol) 3,5-dimethyl-4-hydroxybenzonitrile (commercially available) and 0.29 ml (1.17 mmol) tri-N-butylposphine in 8 ml tetrahydrofuran, 0.20 g (1.17 mmol) N′N′N′N-tetramethylazodicarboxylate were added in one portion. After 48 h stirring at RT another 0.29 ml (1.17 mmol) tri-N-butylposphine and 0.2 g (1.17 mmol) N′N′N′N-tetramethylazodicarboxylate were added. The reaction mixture was stirred at RT for another 5 days, silica gel was added and the suspension evaporated to dryness. The residue was chromatographed three times using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane and tert-butyl methyl ether (100:0 to 60:40) to give the desired compound as a light yellow solid (22%). MS (Turbo Spray): m/z=520.3 [M+H].

Aufarbeitung

  1. additionwere added
  2. additionsilica gel was added
  3. customthe suspension evaporated to dryness
  4. customThe residue was chromatographed three times
  5. washeluting with a gradient of heptane and tert-butyl methyl ether (100:0 to 60:40)

Quellen und Nachweise

ORD-Eintrag
ord-3d60b0fe287842b09153016ec14f558a
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08088930B2

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