GS-5818 interMediate

1378388-19-2

1378388-20-5

General procedure for the synthesis of 3-chloro-10,11-dihydro-5H-dibenzo[c,g]chroman-8(9H)-one from 7-[(2-bromo-5-chlorophenyl)methoxy]-3,4-dihydro-1(2H)-naphthalenone: To a 1L flask was added palladium(II) pivalate neopentanoate (1.18 g, 3.8 mmol), tris(4-fluorophenyl)phosphine (1.20 g. 3.8 mmol), pivalic acid (2.33 g, 22.8 mmol), and potassium carbonate (31.8 g, 228 mmol), followed by a solution of 7-[(2-bromo-5-chlorophenyl)methoxy]-3,4-dihydro-1(2H)-naphthalenone (27.8 g, 76.2 mmol) in dimethylacetamide (380 mL). The flask was evacuated and backfilled with argon and the process was repeated five times. The reaction mixture was stirred at 60 °C for 24 h under argon protection. Upon completion of the reaction, it was cooled to room temperature and diluted with methyl tert-butyl ether (MTBE) and water. The resulting two-phase mixture was stirred for 3 hours, filtered through diatomaceous earth and washed with MTBE. The organic layer of the filtrate was separated and washed sequentially twice with water and once with brine. The organic layer was dried with magnesium sulfate, filtered, concentrated and purified by fast column chromatography (hexane/dichloromethane) to afford 3-chloro-10,11-dihydro-5H-dibenzo[c,g]chroman-8(9H)-one (14.4 g, 67% yield) as an off-white solid.