Chloromethyl Methyl Ether → 2,3-Dihydro-6-bromo-5-benzofuranol methoxymethyl ether

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Reaction Steps

A flame-dried 1000 mL 3-neck flask fitted with an internal thermometer, magnetic stirring, and a 250 mL dropping funnel was charged with sodium hydride (60% dispersion in mineral oil, 11.17 g, 279 mmol) and dimethylformamide (dried over molecular sieves, 200 mL). A solution of 16 (50.00 g, 233 mmol) in dimethylformamide (100 mL) was added dropwise such that the reaction temperature did not exceed 40° C (addition time was approximately 30 minutes). When hydrogen evolution had ceased, an ice bath was added and chloromethyl methylether (22.47 g, 297 mmol) was added dropwise at 25° C. Upon completion of the addition the reaction mixture was allowed to stir at room temperature for two hours then quenched by pouring into water (1000 mL). The mixture was extracted with ether (3×300 mL) and the combined organic extracts washed sequentially with water (2×500 mL) and 20% NaCl (300 mL), dried (Na2SO4), and concentrated. Distillation afforded 17 as a colorless liquid.

Provenance & Evidence