Acetone → (+/-)-(E)-1-[4,5-Bis(4-fluorophenyl)-2-(1-methylethyl)-1H-imidazol-1-yl]-3-hydroxy-1-hexen-5-one

HRID 892968

Reaktionsgleichung

Reaktionsgleichung von HRID 892968
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH3:11][C:12]([CH3:14])=[O:13].[F:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[N:23]=[C:24]([CH:38]([CH3:40])[CH3:39])[N:25](/[CH:34]=[CH:35]/[CH:36]=[O:37])[C:26]=2[C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=2)=[CH:18][CH:17]=1>C1COCC1>[F:15][C:16]1[CH:17]=[CH:18][C:19]([C:22]2[N:23]=[C:24]([CH:38]([CH3:40])[CH3:39])[N:25](/[CH:34]=[CH:35]/[CH:36]([OH:37])[CH2:11][C:12](=[O:13])[CH3:14])[C:26]=2[C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=2)=[CH:20][CH:21]=1

Komponenten

5

Edukt 3

HCID 180AcetoneHCID 2733832Lithium HexamethyldisilazideHCID 14849786(E)-3-[4,5-bis(4-fluorophenyl)-2-(1-methylethyl)-1H-imidazol-1-yl]-2-propenal

Produkt 1

HCID 14849826(+/-)-(E)-1-[4,5-Bis(4-fluorophenyl)-2-(1-methylethyl)-1H-imidazol-1-yl]-3-hydroxy-1-hexen-5-one

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To a solution of lithium bis(trimethylsilyl)amide (4.1 ml, IM solution in THF) in dry THF (20 ml) at -78° under nitrogen was added dry acetone (275 μl). After 25 min, a solution of (E)-3-[4,5-bis(4-fluorophenyl)-2-(1-methylethyl)-1H-imidazol-1-yl]-2-propenal (881 mg) in dry THF (15 ml) was added dropwise over 10 min. Stirring was continued for 25 min at -78° then the reaction was quenched with saturated aqueous ammonium chloride solution (25 ml) and allowed to warm to room temperature. The layers were separated and the aqueous phase extracted with ethyl acetate (2×50 ml). The combined extracts were dried and evaporated to a white solid (1.09 g). FCC eluting with System A (1:1) gave the title compounds as a white solid (709.6 mg). (CDCl3) 7.35-7.45 and 7.20-7.29(2m,4H,C-2 and C-6 protons of 4-fluorophenyl), 7.10 and 6.90(2t,4H,C-3 and C-5 protons of 4-fluorophenyl,J=9 Hz), 6.70(d,1H,NCH=CHCH,J=13.7 Hz), 5.26(dd,1H,NCH=CHCH,J=13.7 Hz,6.3 Hz), 4.58(m,1H,NCH=CHCH), 3.15(m,2H,CH(CH3)2 and OH), 2.50(m,2H,CH(OH)CH2C(O)), 2.15(s,3H,CH2C(O)CH3), 1.40(d,6H,CH(CH3)2,J=7.5 Hz).

Aufarbeitung

  1. waitwas continued for 25 min at -78°
  2. customthe reaction was quenched with saturated aqueous ammonium chloride solution (25 ml)
  3. customThe layers were separated
  4. extractionthe aqueous phase extracted with ethyl acetate (2×50 ml)
  5. customThe combined extracts were dried
  6. customevaporated to a white solid (1.09 g)
  7. washFCC eluting with System A (1:1)

Quellen und Nachweise

ORD-Eintrag
ord-878e564eb77540528861c9b79c13ff26
Quelldatensatz
uspto-grants-1992_06
Patentnummer
US05120848

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