p-Toluenesulfonic acid → 2a-Methyl-1,2,2a,5-tetrahydropyrrolo[4,3,2-de]quinolin-4(3H)-one

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Reaction Steps

A mixture of (±)-ethyl (4-amino-3-methyl-2,3-dihydro-1H-indol-3-yl)acetate from Step B (2.50 g, 10.7 mmol) and p-toluenesulfonic acid (2 mg, 0.01 mmol) was heated in xylenes (50 mL) at reflux for 13 h, then concentrated to dryness under reduced pressure. The crude product was purified by silica gel chromatography, eluting with a gradient of CH2Cl2:MeOH:N4OH—100:0:0 to 90:4.5:0.5, to give the racemic title compound. The enantiomers were resolved by HPLC, utilizing a ChiralPak AD column and eluting with hexane:i-PrOH:Et2NH—75:25:0.1. The first major peak to elute was 2a-methyl-1,2,2a,5-tetrahydropyrrolo[4,3,2-de]quinolin-4(3H)-one, enantiomer A, the title compound, and the second major peak to elute was 2a-methyl-1,2,2a,5-tetrahydropyrrolo[4,3,2-de]quinolin-4(3H)-one, enantiomer B. MS: m/z=189 (M+1).

Provenance & Evidence