Reaktion #158214

Reaktionsgleichung

isatine

5-iodo-isatin

malonic acid

pyridine

triethyl amine

pyridinium (3-hydroxy-5-iodo-2-oxo-2,3-dihydro-1H-indol-3-yl)-acetate

dimethyl carbamoyl chloride

→

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

Lösungsmittel

ethyl acetate

ethyl acetate

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeprecipitation of the latter salt starts, and when the mixture
2. 2
   workup.ADDITIONa suspension of the salt in an orange solution
3. 3
   Sonstigehas formed
4. 4
   workup.DISSOLUTIONthe salt dissolves
5. 5
   Sonstigeto give a dark solution
6. 6
   SonstigeA solid starts to precipitate
7. 7
   workup.STIRRINGthe mixture is stirred for another 2 hours at 80° C
8. 8
   workup.ADDITIONThen 4 N HCl is added (350 mL)
9. 9
   workup.STIRRINGstirring
10. 10
    FiltrationThe mixture is then filtered
11. 11
    Waschenthe filter cake is washed with 50% ethanol
12. 12
    TrocknenAfter drying 72.6 g (70.5%) of a grayish powder of the title compound, mp.=246° C

Vorschrift

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 the with water. After drying 72.6 g (70.5%) of a grayish powder of the title compound, mp.=246° C. 1H-NMR (DMSO-D6, 300 MHz) δ 2.62, 2.91 (2 s, 3 each, N(CH3)2); 2.91, 3.25 (AB, 2H, |2J|=16.4 Hz, CH2); 5.97 (br s, 1H, OH); 6.59 (d, 1H, 3J=7.9 Hz, H-7); 7.46 (dd, 1H, 4J=1.5 Hz, H-6); 7.54 (d, 1H, H-4); 10.15 (br s, 1H, NH). 13C-NMR (DMSO-D6, 75 MHz) δ 35.08, 37.48 (N(CH3)2); 40.86 (CH2); 73.76 (C-3); 84.29 (C-5); 112.49 (C-7); 132.44 (C-4); 136.06 (C-9); 137.72 (C-6); 143.66 (C-8); 168.93 CONMe2); 178.47 (C-2).

Quelle