Beta-Lapachone → HCID 58601388, compound

Participants

Reaction Steps

The compound 5-(acetyloxy)-2,2-dimethyl-3,4-dihydro-2H-benzo[h]chromen-6-yl N-(tert-butoxycarbonyl)-2-methylalaninate (27) is synthesized as described in scheme 1a using zinc dust (2.0 g, 30.5 mmol), 2,2-dimethyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione (2.0 g, 8.26 mmol), Na2S2O4 (5.75 g, 33.0 mmol), N-(tert-butoxycarbonyl)-2-methylalanine (3.36 g, 16.51 mmol), triethylamine (1.04 mL, 7.43 mmol), HBTU (6.26 g, 16.5 mmol) and DMF (30 mL) for the 1st step. The acetylation step is carried out using zinc dust (1.0 g, 15.3 mmol), thriethylamine (1.04 mL, 7.43 mmol) and acetic anhydride (20 mL). Both the compounds are generated in the reaction. The crude mixture is purified by two consecutive flash column chromatography (SiO2, 1st using a gradient from 100% dichloromethane to 2% EtOAc in dichloromethane and 2nd using a gradient from 10% EtOAc in hexanes to 25% EtOAc in hexanes) to afford pure desired single isomer product (0.405 g, %) as a white solid. 400 MHz 1H NMR (CDCl3) δ: 8.19 (d, J=8.8 Hz, 1H), 7.85 (d, J=7.6 Hz, 1H), 7.50-7.35 (m, 2H), 5.19 (br. s, 1H), 2.67 (t, J=6.6 Hz, 2H), 2.37 (s, 3H), 1.87 (t, J=6.8 Hz, 2H), 1.78 (s, 6H), 1.47 (s, 9H), 1.42 (s, 6H); LCMS: 472 [M+H].

Provenance & Evidence