Iodine → 5-Chloro-3-[5-(5,5-dimethyl-[1,3]dioxan-2-yl)-2-methoxyphenyl]-3-hydroxy-1,3-dihydroindol-2-one

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Reaction Steps

Magnesium shavings (2.2 g, 89 mmol) were placed in THF (30 mL) and etched with several iodine crystals. A solution of 2-(3-bromo-4-methoxyphenyl)-5,5-dimethyl[1,3]dioxane (26.0 g, 86 mmol) in THF (80 mL) was added thereto, with stirring. After initiation of the reaction (identifiable by the exothermic evolution of heat), the rate of dropwise addition was decreased so that the reaction mixture was just at the boiling point. The reaction mixture was stirred for an additional 20 min and then was cooled to room temperature. The Grignard solution thus obtained was pumped into an ice-cold solution of the 5-chlorisatin sodium salt (prepared by treating a solution of 5-chlorisatin (13.1 g, 72 mmol) in THF (400 mL) with one equivalent of sodium hydride for one hour at 0° C.), and was then stirred for 5 hours at room temperature. The reaction solution was combined with aqueous ammonium chloride solution, with stirring, and the batch was extracted twice with ethyl acetate. The combined organic phase was washed with water and saturated sodium chloride solution, dried over magnesium sulfate, and concentrated under reduced pressure. Treatment of the residue with diethyl ether resulted in crystallization of the desired product. Yield: 19.2 g (66%) of a white solid. MS (API-ES, pos) m/z=386 [M+H—H2O]+.

Provenance & Evidence