Sodium hydride → 1-{[3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxiran-2-yl]methyl}-2-iodo-1H-imidazole

HRID 508119Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 508119
[H-].[Na+].[I:3][C:4]1[NH:5][CH:6]=[CH:7][N:8]=1.Br[CH2:10][C:11]1([C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:22]=2[F:28])[CH:13]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[Cl:20])[O:12]1>CN(C=O)C.O>[Cl:20][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[CH:13]1[O:12][C:11]1([CH2:10][N:5]1[CH:6]=[CH:7][N:8]=[C:4]1[I:3])[C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:22]=1[F:28]

Komponenten

6

Edukt 3

HCID 24758Sodium hydrideHCID 27734682-iodo-1H-imidazoleHCID 895876022-(Bromomethyl)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxirane

Produkt 1

HCID 895954751-{[3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxiran-2-yl]methyl}-2-iodo-1H-imidazoleAusbeute 72 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

At 3° C., sodium hydride (60% by weight strength dispersion in mineral oil, 56.7 mg, 1.41 mmol) was added to a stirred solution of 2-iodoimidazole (242 mg, 1.25 mmol) in dry DMF (8 ml). The reaction mixture was stirred at room temperature for 20 min, and 2-(bromomethyl)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxirane (300 mg, 0.83 mmol) in dry DMF (4 ml) was then added. The resulting mixture was stirred at 50° C. for 20 h and then at 80° C. for 3 h. After cooling to room temperature, the reaction mixture was diluted with water and extracted with AcOEt, and the extracts were dried and concentrated to dryness under reduced pressure. The filtrates were combined and concentrated to dryness under reduced pressure. Purification of the residue on silica gel gave 1-{[3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxiran-2-yl]methyl}-2-iodo-1H-imidazole as a 55/45 mixture of diastereoisomers [298 mg, colourless solid, yield 72%; HPLC/MS: m/z=473 (M+H); log P(HCOOH)=2.92 (major diastereoisomer), 3.31 (minor diastereoisomer)].

Aufarbeitung

  1. stirringThe resulting mixture was stirred at 50° C. for 20 h
  2. waitat 80° C. for 3 h
  3. temperatureAfter cooling to room temperature
  4. extractionextracted with AcOEt
  5. customthe extracts were dried
  6. concentrationconcentrated to dryness under reduced pressure
  7. concentrationconcentrated to dryness under reduced pressure
  8. customPurification of the residue on silica gel

Quellen und Nachweise

ORD-Eintrag
ord-9449f384e17a41aab20d4e096d4e39d5
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09095136B2

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