Methanol → 8-Chloro-6-(2-fluorophenyl)-1,2-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepin-1-one

HRID 614986Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 614986
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:12](=[O:19])[NH:13][C:14](C(OC)=O)=[C:10]3[CH2:9][N:8]=[C:7]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[F:26])[C:6]=2[CH:27]=1.CO.[OH-].[K+]>O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:12](=[O:19])[NH:13][CH:14]=[C:10]3[CH2:9][N:8]=[C:7]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[F:26])[C:6]=2[CH:27]=1

Komponenten

5

Edukt 3

HCID 887MethanolHCID 14797Potassium HydroxideHCID 867361538-chloro-1,2-dihydro-6-(2-fluorophenyl)-1-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylic acid, methyl ester

Produkt 1

HCID 149357748-Chloro-6-(2-fluorophenyl)-1,2-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepin-1-one

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Versuchsvorschrift

A mixture of 0.386 g (1 mmole) of 8-chloro-1,2-dihydro-6-(2-fluorophenyl)-1-oxo-4H-imidazo[1,5-a] [1,4]benzodiazepine-3-carboxylic acid, methyl ester, 10 ml of methanol, 1 ml of water and 0.225 g (4 mmole) of potassium hydroxide was heated to reflux for 31/2 hours under an atmosphere of nitrogen. The solvent was evaporated and the residue was acidified with acetic acid and extracted with methylene chloride. The extracts were dried and evaporated and the residue was heated in mineral oil up to 230° for 5 min. The reaction mixture was partitioned between 1N hydrochloric acid and methylene chloride/hexane. The acid extract was made alkaline with sodium carbonate solution and extracted with methylene chloride. The residue obtained after evaporation of the dried extracts was chromatographed over 10 g of silica gel using methylene chloride/ethyl acetate 1:2. Crystallization of the combined clean fractions from ethyl acetate/hexane yielded colorless crystals with mp 247°-250°. Uv λmax 212 mμ (ε=42250) sh 262 (10000) ir (KBr) 1695 cm-1 (CO) 3150 (NH). Nmr (CDCl3) 4.18 ppm (d, 1) and 4.88 (d, 1) (AB-system, J=12.5 Hz, C4 -H) 6.28 (d, 1, J=2 Hz, C3 -H) 6.9-7.7 (m, 5, aromatic H) 8.13 (d, 1, J=8.5 Hz, C10 -H) 10.46 (broad s, 1, NH).

Aufarbeitung

  1. temperaturewas heated
  2. temperatureto reflux for 31/2 hours under an atmosphere of nitrogen
  3. customThe solvent was evaporated
  4. extractionextracted with methylene chloride
  5. customThe extracts were dried
  6. customevaporated
  7. temperaturethe residue was heated in mineral oil up to 230° for 5 min
  8. customThe reaction mixture was partitioned between 1N hydrochloric acid and methylene chloride/hexane
  9. extractionThe acid extract
  10. extractionextracted with methylene chloride
  11. customThe residue obtained
  12. customafter evaporation of the dried extracts
  13. customwas chromatographed over 10 g of silica gel
  14. customCrystallization of the combined clean fractions from ethyl acetate/hexane yielded colorless crystals with mp 247°-250°

Quellen und Nachweise

ORD-Eintrag
ord-adf84810982f44949e93b228e755ad11
Quelldatensatz
uspto-grants-1979_03
Patentnummer
US04146722

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