Glycerol → 7-Bromo-8-fluoroquinoline

Participants

Reaction Conditions

Reaction Steps

A 500 mL round bottom flask equipped with a stirbar and air-condenser was charged with 3-bromo-2-fluoroaniline (10.00 g, 52.6 mmol), sodium 3-nitrobenzenesulfonate (21.13 g, 94 mmol), and propane-1,2,3-triol (glycerol) (13.57 g, 147 mmol). The mixture was taken up in water (11.38 mL), carefully treated with conc. sulfuric acid (21.06 mL), and then heated to 150° C. with stirring for 2 h. The reaction was then cooled to room temperature and the flask fitted with an ice bath. The reaction mixture was carefully neutralized with 5N aq sodium hydroxide (˜180 mL). The mixture was then allowed to stir for 20 min, checked for neutral pH, and then diluted with dichloromethane (1000 mL). The entire mixture was transferred to a separatory funnel and the resulting emulsion was treated with ˜200 mL saturated brine and allowed to stand overnight to separate the layers. The organic layer was isolated and the aqueous layer was extracted with an additional quantity of dichloromethane (˜400 mL). The organics were then pooled, washed with 400 mL 1N aq sodium hydroxide solution, dried over sodium sulfate, filtered, and concentrated to a residue. The residue solidified under high vacuum to afford the title compound as a dark brown solid (9.16 g, 75% yield). MS(ES)+ m/e 225.9, 227.8 [M+H]+.

Provenance & Evidence