Diisobutylaluminum hydride → Ammonium Hydroxide

Participants

Reaction Steps

To a solution of (±)-tert-butyl (2,4-dioxo-1,2,4,5-tetrahydropyrrolo[4,3,2-de]quinolin-2a(3H)-yl)methylcarbamate from Step C (1.20 g, 3.78 mmol) in THF (20 mL) at 0° C. was added DIBAL-H (18.9 mL of a 1 M solution in toluene, 18.9 mmol). The reaction mixture was stirred for 2 h and then quenched by the slow addition of saturated aqueous sodium potassium tartrate (100 mL) and extracted with EtOAc (3×50 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of CH2Cl2:MeOH:NH4OH—100:0:0 to 95:5:1, to give (±)-tert-butyl [(2-oxo-1,2,4,5-tetrahydropyrrolo[4,3,2-de]quinolin-2a(3H)-yl)methyl]carbamate, which eluted first, and the racemic title compound, which eluted second. The enantiomers were resolved by HPLC, utilizing a ChiralPak AD column and eluting with hexane:EtOH:Et2NH—60:40:0.1. The first major peak to elute was tert-butyl [(4-oxo-1,2,4,5-tetrahydropyrrolo[4,3,2-de]quinolin-2a(3H)-yl)methyl]carbamate, enantiomer A, the title compound, and the second major peak to elute was tert-butyl [(4-oxo-1,2,4,5-tetrahydropyrrolo[4,3,2-de]quinolin-2a(3H)-yl)methyl]carbamate, enantiomer B. MS: m/z=304 (M+1).

Provenance & Evidence