Niclosamide → HCID 68760257, Verbindung

HRID 1509841

Reaktionsgleichung

Reaktionsgleichung von HRID 1509841
[CH3:1][C:2]1([CH3:12])[O:6][C@H:5]([CH2:7][C:8]([OH:10])=[O:9])[C:4](=[O:11])[O:3]1.C(Cl)(=O)C(Cl)=O.CN(C)C=O.[Cl:24][C:25]1[CH:26]=[CH:27][C:28](O)=[C:29]([CH:43]=1)[C:30]([NH:32][C:33]1[CH:38]=[CH:37][C:36]([N+:39]([O-:41])=[O:40])=[CH:35][C:34]=1[Cl:42])=[O:31]>C(Cl)(Cl)Cl.N1C=CC=CC=1>[CH3:1][C:2]1([CH3:12])[O:6][C@H:5]([CH2:7][C:8]([O:10][C:28]2[CH:27]=[CH:26][C:25]([Cl:24])=[CH:43][C:29]=2[C:30](=[O:31])[NH:32][C:33]2[CH:38]=[CH:37][C:36]([N+:39]([O-:41])=[O:40])=[CH:35][C:34]=2[Cl:42])=[O:9])[C:4](=[O:11])[O:3]1

Komponenten

7

Edukt 4

HCID 4477NiclosamideHCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 108449602-((4R)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl)acetic acid

Produkt 1

HCID 68760257HCID 68760257, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1049PyridineLösungsmittelHCID 6212ChloroformLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

A suspension of (R)-(−)-2,2-Dimethyl-5-oxo-1,3-dioxolane-4-acetic acid (Sigma-Aldrich, St. Louis, Mo.) (2.17 g, 12.46 mmol) in chloroform (24 mL) was treated with oxalyl chloride (2.11 mL, 25 mmol) and a drop of N,N-dimethylformamide was added. The progression of reaction was monitored by the observation of gas evolution by means of a bubbler. After 2 hours at room temperature, the reaction mixture was warmed to 50° C. for 2 hours, cooled to room temperature, and concentrated to remove volatiles. This residue was diluted with chloroform (10 mL) and added to a suspension of 5-Chloro-N-(2-chloro-4-nitrophenyl)-2-hydroxybenzamide (2.04 g, 6.23 mmol) in pyridine (30 mL) in which 4-dimethylaminopyride (20 mg) had been previously dissolved. The reaction mixture was stirred at room temperature for 16 h and then was partitioned between 1N aqueous HCl and ethyl acetate. The ethyl acetate solution was dried over magnesium sulfate and concentrated to a dark oil. The residue was dissolved in chloroform and placed upon a short column of silica gel (60 mm i.d.×15 mm). The product was eluted with chloroform and concentrated to an oil. The product was crystallized with a mixture of hexanes and ethyl acetate. 1HNMR (300 MHz, DMSO-d6): δ1.456 (s, 3H), 1.495 (s, 3H), 4.939 (m, 1H), 7.352 (d, J=9 Hz, 1H, H3), 7.730 (dd, J=3.9 Hz, 1H, H4), 7.851 (d, J=3 Hz, 1H, H6), 8.110 (d, J=9 Hz, 1H, H6′), 8.255 (dd, J=3, 9 Hz, 1H, H5′), 8.411 (d, J=3 Hz, 1H, H3′), 10.481 (s, 1H, NH).

Aufarbeitung

  1. customThe progression of reaction
  2. temperaturecooled to room temperature
  3. concentrationconcentrated
  4. customto remove volatiles
  5. additionThis residue was diluted with chloroform (10 mL)
  6. dissolutionhad been previously dissolved
  7. customwas partitioned between 1N aqueous HCl and ethyl acetate
  8. dry with materialThe ethyl acetate solution was dried over magnesium sulfate
  9. concentrationconcentrated to a dark oil
  10. dissolutionThe residue was dissolved in chloroform
  11. washThe product was eluted with chloroform
  12. concentrationconcentrated to an oil
  13. customThe product was crystallized with a mixture of hexanes and ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-24a5b20d655547febe52d9843ad2dd96
Quelldatensatz
uspto-grants-2012_07
Patentnummer
US08211882B2

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