Hydrochloric Acid → 3-(4'-Chloro-3'-fluoro-4-methylbiphenyl-3-yl)-4-hydroxy-1-azaspiro[4.5]dec-3-en-2-one

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Reaction Steps

Under argon, 36.4 mg (0.05 mmol) of dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium complex were added to 150 mg (0.45 mmol) of the compound from Example 13A in 15 ml of degassed 1,2-dimethoxyethane. The mixture was stirred at room temperature for 5 minutes, and 117 mg (0.67 mmol) of (4-chloro-3-fluorophenyl)boronic acid and a solution of 509 mg (1.56 mmol) of caesium carbonate in 0.9 ml of degassed water was then added. Under microwave irradiation, the reaction mixture was heated at 150° C. for 10 minutes. After cooling, 0.3 ml of concentrated aqueous hydrogen chloride solution were added, magnesium sulphate was added, the mixture was filtered through silica gel, the filter cake was washed with ethyl acetate and the mixture was concentrated. Purification of the crude product by HPLC chromatography (C18 phase, mobile phase: water/acetonitrile gradient/0.1% formic acid) gave 43.7 mg (25% of theory) of the title compound.

Provenance & Evidence