Methyl chloroformate → HCID 22219595, compound

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Reaction Steps

Methyl chloroformate (120 mL, 1.53 mol) is added dropwise to 2,3,4,5-tetrahydro-1H-3-benzazepine (J. Heterocyclic Chem., 1971, 779-783) in THF (1 L), water (1 L), and sodium bicarbonate (206 g, 2.46 mmol) at 0° C. The mixture is stirred at room temperature for 4 h, extracted with dichloromethane which is washed with 1 N hydrochloric acid, water, 1 N sodium hydroxide, and brine then dried over anhydrous sodium sulfate, filtered, and concentrated to a amber oil which slowly crystallized. The solid is dissolved in concentrated sulfuric acid (500 mL), cooled to −10° C., and treated dropwise with a solution of ammonium nitrate (82 g, 1.03 mol) in concentrated sulfuric acid (500 mL). The temperature is maintained at 0-5° C. for 3 h then poured onto ice and extracted with dichloromethane. The organic layer is washed with water, saturated aqueous sodium bicarbonate, dried over anhydrous sodium sulfate, filtered, concentrated, and chromatographed on a Chiralcel® AD column with 20% isopropanol in heptane to give 161 g (66%) of the title compound.

Provenance & Evidence