1,2-Dibromoethane → N-tert-butoxycarbonyl 1-(5-fluorobenzofur-7-yl)-2-aminopropane

Participants

Reaction Conditions

Reaction Steps

A mixture of 19 gm (88.8 mMol) 5-fluoro-7-bromobenzofuran and 4.7 gm (193.3 mMol) magnesium turnings in 300 mL diethyl ether was stirred at 40° C. while 7.6 mL (88.2 mMol) 1,2-dibromoethane were added dropwise over 15 minutes. Thirty minutes after the addition was complete, the reaction mixture was cooled to −10° C. To this cooled mixture were then added 6.76 gm (32.8 mMol) copper(I) bromide-dimethylsulfide complex all at once followed by the dropwise addition of 13 gm (82.8 mmol) of N-tert-butoxycarbonyl-2-methylaziridine and 20 mL diethyl ether. The resulting mixture was stirred for 2 hours at −10–0° C. The reaction mixture was then diluted 1.5 L ethyl acetate and 150 mL of water. The resulting slurry was filtered through a pad of celite and the celite pad was washed with two 150 ml portions of ethyl acetate. The filtrate was separated and the organic phase was extracted with two 200 mL portions of water and one 200 mL portion of saturated aqueous sodium chloride. The remaining organic phase was then dried over magnesium sulfate and concentrated under reduced pressure. The residue was crystallized from hexane containing 20% ethyl acetate. This solid was subjected to silica gel chromatography, eluting with a gradient of hexane containing from 0–20% ethyl acetate. Fractions containing product were combined and concentrated under reduced pressure. The residue was crystallized from hexane to provide 13.5 gm (56%) of the desired compound.

Provenance & Evidence