(+/-)-Ethyl (4-amino-3-methyl-2-oxo-2,3-dihydro-1H-indol-3-yl)acetate → Ammonium Hydroxide

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Reaction Steps

A mixture of (±)-ethyl (4-amino-3-methyl-2-oxo-2,3-dihydro-1H-indol-3-yl)acetate from Step C (2.37 g, 9.56 mmol) and AcOH (1 mL) was heated in xylenes (10 mL) at reflux for 24 h, then concentrated to dryness under reduced pressure. The crude product was partially purified by silica gel chromatography, eluting with a gradient of CH2Cl2:MeOH:NH4OH—100:0:0 to 90:9:1, to give a crude sample of the title compound. Further purification by silica gel chromatography, eluting with a gradient of CH2Cl2:EtOAc—100:0 to 0:100, gave the racemic title compound. The enantiomers were resolved by HPLC, utilizing a ChiralPak AS column and eluting with hexane:EtOH—70:30. The first major peak to elute was 2a-methyl-2a,5-dihydropyrrolo[4,3,2-de]quinoline-2,4(1,3H)-dione, enantiomer A, and the second major peak to elute was 2a-methyl-2a,5-dihydropyrrolo[4,3,2-de]quinoline-2,4(1H,3H)-dione, enantiomer B, the title compound. MS: m/z=203 (M+1).

Provenance & Evidence