Hydrochloric Acid → 8-(3,5-Difluorophenyl)-1,4-dioxaspiro[4.5]decan-8-ol

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Reaction Steps

In an argon atmosphere, 20.3 g of magnesium was suspended in THF (40 mL), and a solution of 3,5-difluorobromobenzene (149 g) in THF (450 mL) was added dropwise to the resultant suspension at an inside temperature of 40 to 65° C. After stirring at room temperature for 1 hour, a solution of 1,4-cyclohexanedione monoethylene ketal (100 g) in THF (300 mL) was added dropwise at an inside temperature of 40 to 60° C., followed by stirring at room temperature for 1 hour. Then, water (250 mL), 10% hydrochloric acid (200 mL), and 750 mL of toluene were added in that order, and the mixture was stirred at room temperature for 30 minutes to separate an organic layer. The organic layer was washed with saturated brine two times, and then dried with anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to yield 178 g of 4-(3,5-difluorophenyl)-4-hydroxycyclohexanone ethylene ketal as a light yellow solid.

Provenance & Evidence