Reaktion #1140913

Reaktionsgleichung

triethylamine

3-aminophthalic acid hydrochloride

3-aminoglutarimide hydrochloride

acetic acid

3-aminophthalic acid

→

4-Amino-2-(2,6-dioxo-3-piperidinyl)isoindole-1,3-dione

Lösungsmittel

water

acetonitrile

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwas charged into a reaction vessel
2. 2
   workup.STIRRINGNext, the reaction mixture was stirred further for 10-15 minutes
3. 3
   Temperaturrefluxed at about 85 to 87° C. for about 5 to 7 hours
4. 4
   TemperaturAfter the reaction mixture was cooled to about 20 to 25° C. over 1-2 hours
5. 5
   workup.STIRRINGThe resulting mixture was stirred at about 15 to 20° C. for about 20 to 30 minutes
6. 6
   Sonstigeto provide a yellow solid precipitate, which
7. 7
   Filtrationwas filtered
8. 8
   Waschenwashed with DI water (3×1.0 L) and acetonitrile (2×500 mL)
9. 9
   Sonstigedried at about 35 to 40° C. in vacuo to a constant weight at 210.0 g (84%)

Vorschrift

A mixture of 3-aminophthalic acid hydrochloride (200 g, 0.92 mol, from Prosynth Ltd., Suffolk, UK), 3-aminoglutarimide hydrochloride (159 g, 0.96 mol, from Evotec OAI, Hamburg, Germany), acetonitrile (2.0 L), and acetic acid (577 g, 9.6 mol, from Fisher Scientific) was charged into a reaction vessel. After the mixture was stirred for 15 minutes, triethylamine (465.0 g, 4.6 mol, from Aldrich, Milwaukee, Wis.) was added dropwise over 30-35 minutes while the reaction temperature was maintained at 20-25° C. Next, the reaction mixture was stirred further for 10-15 minutes and then refluxed at about 85 to 87° C. for about 5 to 7 hours or until the in-process control, i.e., HPLC AP at 240 nm, indicates that <2% of the 3-aminophthalic acid remained in the reaction mixture. After the reaction mixture was cooled to about 20 to 25° C. over 1-2 hours, 1.0 L of water was charged over 15-30 minutes at about 20 to 25° C. The resulting mixture was stirred at about 15 to 20° C. for about 20 to 30 minutes to provide a yellow solid precipitate, which was filtered, washed with DI water (3×1.0 L) and acetonitrile (2×500 mL), and then dried at about 35 to 40° C. in vacuo to a constant weight at 210.0 g (84%).

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