Malonic Acid → 2-(3-Hydroxy-5-iodo-2-oxo-2,3-dihydro-1H-indol-3-yl)-N,N-dimethyl-acetamide

HRID 507366Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 507366
[I:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2=[O:12].[C:13]([OH:19])(=O)[CH2:14]C(O)=O.[N:20]1[CH:25]=CC=C[CH:21]=1.N1C2C(=CC=CC=2)C(=O)C1=O.OC1(CC([O-])=O)C2C(=CC=C(I)C=2)NC1=O.[NH+]1C=CC=CC=1.C(N(CC)CC)C.CN(C)C(Cl)=O>C(OCC)(=O)C>[OH:12][C:5]1([CH2:14][C:13]([N:20]([CH3:25])[CH3:21])=[O:19])[C:4]2[C:8](=[CH:9][CH:10]=[C:2]([I:1])[CH:3]=2)[NH:7][C:6]1=[O:11]

Komponenten

9

Edukt 7

HCID 867Malonic AcidHCID 1049PyridineHCID 6598Dimethylcarbamoyl ChlorideHCID 7054IsatinHCID 8471TriethylamineHCID 886955-IodoisatinHCID 67148240pyridinium (3-hydroxy-5-iodo-2-oxo-2,3-dihydro-1H-indol-3-yl)-acetate

Produkt 1

HCID 591297532-(3-Hydroxy-5-iodo-2-oxo-2,3-dihydro-1H-indol-3-yl)-N,N-dimethyl-acetamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8857Ethyl AcetateLösungsmittel2×

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A 2 L flask with mechanical stirrer is charged with 5-iodo-isatin (78.1 g, 0.286 mol), malonic acid (35.7 g, 0.343 mol), and pyridine (90.4 g, 1.144 mol). The mixture is heated to 80° C. When most of the isatine has dissolved, ethyl acetate (100 mL) is added to prevent blocking of the stirrer by the precipitating pyridinium (3-hydroxy-5-iodo-2-oxo-2,3-dihydro-1H-indol-3-yl)-acetate. After 1 hour, precipitation of the latter salt starts, and when the mixture has been kept stirring for another 2 hours, a suspension of the salt in an orange solution has formed. To this is added triethyl amine (43.3 g, 0.429 mol), and the salt dissolves to give a dark solution. Then a solution of dimethyl carbamoyl chloride (40 g, 0.372 mol) in ethyl acetate (50 mL) is added dropwise during 20 minutes. A solid starts to precipitate, and the mixture is stirred for another 2 hours at 80° C. Then 4 N HCl is added (350 mL), and stirring is continued for 30 additional minutes in order to hydrolyze any excess carbamoyl chloride. The mixture is then filtered, and the filter cake is washed with 50% ethanol and then with water. After drying 72.6 g (70.5%) of a grayish powder of the title compound, mp.=246° C.

Aufarbeitung

  1. customprecipitation of the latter salt starts, and when the mixture
  2. additiona suspension of the salt in an orange solution
  3. customhas formed
  4. dissolutionthe salt dissolves
  5. customto give a dark solution
  6. customA solid starts to precipitate
  7. stirringthe mixture is stirred for another 2 hours at 80° C
  8. additionThen 4 N HCl is added (350 mL)
  9. stirringstirring
  10. filtrationThe mixture is then filtered
  11. washthe filter cake is washed with 50% ethanol
  12. dry with materialAfter drying 72.6 g (70.5%) of a grayish powder of the title compound, mp.=246° C.

Quellen und Nachweise

ORD-Eintrag
ord-b0988c81260a4842bb0ba4f7623ce4ba
Quelldatensatz
uspto-grants-2010_08
Patentnummer
US07786156B2

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