Sodium Iodide → HCID 20096977, Verbindung

HRID 1769687Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1769687
Br[CH2:2][C:3]([O:5][CH:6]([C:17]1[CH:22]=[CH:21][C:20]([CH2:23][CH3:24])=[CH:19][CH:18]=1)[C:7]([C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH3:16])=[CH:11][CH:10]=1)=[O:8])=[O:4].C(=O)([O-])[O-].[Na+].[Na+].[I-].[Na+].[CH3:33][C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([CH3:40])[C:35]=1[NH:41][C:42](=[O:50])[CH2:43][N:44]1[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]1>C(#N)C>[CH3:33][C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([CH3:40])[C:35]=1[NH:41][C:42]([CH2:43][N:44]1[CH2:45][CH2:46][N:47]([CH2:2][C:3]([O:5][CH:6]([C:17]2[CH:22]=[CH:21][C:20]([CH2:23][CH3:24])=[CH:19][CH:18]=2)[C:7](=[O:8])[C:9]2[CH:14]=[CH:13][C:12]([CH2:15][CH3:16])=[CH:11][CH:10]=2)=[O:4])[CH2:48][CH2:49]1)=[O:50]

Komponenten

6

Edukt 4

HCID 5238Sodium IodideHCID 10340Sodium CarbonateHCID 2608606Cvt-2738HCID 20096939HCID 20096939, Verbindung

Produkt 1

HCID 20096977HCID 20096977, VerbindungAusbeute 76 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A solution of bromoacetyl chloride (2.00 mL, 24.2 mmol) in anhydrous dichloromethane (20 mL) was added dropwise to a cold (0° C.) mixture of 2-hydroxy-1,2-di-(4-ethylphenyl)ethanone (IX; 6.5 g, 24.2 mmol) and N-methylmorpholine (NMM; 2.7 mL, 24.2 mmol) in anhydrous dichloromethane (180 mL). The mixture was stirred at 0° C. for 1 h and at ambient temperature for 2 h before additional 2-hydroxy-1,2-di-(4-ethylphenyl)ethanone (0.5 mL) and NMM (0.6 mL) were added to aid in completion. After 1 h, the mixture was washed with saturated sodium bicarbonate solution, 1N HCl and brine. Following drying and solvent evaporation, the residue was purified by flash chromatography on silica gel (gradient elution with 10% ethyl acetate in hexanes followed by 25% ethyl acetate in hexanes) and furnished 6.10 g (65%) of bromoacetoxy-1,2-di-(4-ethylphenyl)ethanone as a pale-yellow oil which was carried on directly. A portion of bromoacetoxy-1,2-di-(4-ethylphenyl)ethanone (3.15 g, 8.09 mmol) was treated with anhydrous sodium carbonate (0.86 g, 8.09 mmol), sodium iodide (0.12 g) and N-(2,6-dimethylphenyl)-1-piperazineacetamide (2.0 g, 8.09 mmol) in anhydrous acetonitrile (120 mL) and the resulting mixture was heated to 80° C. for 5 h before it was cooled and concentrated down in vacuo. Purification of the residue by flash chromatography on silica gel with absolute ethyl acetate gave 3.40 g (76%) of 2-oxo-1,2-di-(4-ethylphenyl)ethyl 4-[[[(2,6-dimethylphenyl) amino]carbonyl]-methyl]-1-piperazineacetate as pale-yellow foam. A portion of 2-oxo-1,2-di-(4-ethylphenyl)ethyl 4-[[[(2,6-dimethylphenyl)amino]carbonyl]-methyl]-1-piperazineacetate (2.50 g, 4.50 mmol) was dissolved in glacial acetic acid (75 mL) and ammonium acetate (1.65 g, 22.5 mmol) was added. The mixture was gently refluxed under nitrogen for 6 h before the solvent was removed in vacuo. The residue was partitioned between ethyl acetate and 1N sodium hydroxide solution (until basic) and the organic phase was separated, washed with brine, dried and concentrated. The residue was purified by flash chromatography on silica gel (gradient elution with ethyl acetate followed by 10% methanol in ethyl acetate) and yielded 0.61 g (22%) of the oxazole product I as a white solid and 0.85 g (30%) of the imidazole product I as a white solid after salt formation with ethereal hydrogen chloride.

Aufarbeitung

  1. temperaturewas cooled
  2. concentrationconcentrated down in vacuo
  3. customPurification of the residue by flash chromatography on silica gel with absolute ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-505fbc5e7cfc431eadb3a56bb7a8ce64
Quelldatensatz
uspto-grants-1995_01
Patentnummer
US05382584

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