Bromochloromethane → 6-Fluoro-2-oxiranyl-1-benzopyran

Participants

Reaction Conditions

Reaction Steps

2.5 g of bromochloromethane (19 mmol) were added at room temperature to a solution of 2.0 g of crude 6-Fluoro-1-benzopyran-2-carboxylic acid methyl ester (9.5 mmol) in 40 ml of THF. The solution was then cooled to −80/−85° C. and 7.8 ml of 2.5 M n-BuLi in hexane (19.5 mmol) were slowly added to maintain the internal temperature between −75° C. and −80° C. The reaction progress was monitored by TLC. A 1 M solution of BH3 in THF (10 ml, 10 mmol) was then slowly added to maintain the internal temperature between −70° C. and −80° C. The reaction progress was monitored by TLC. The mixture was hydrolyzed by the addition of water (15 ml) at 0° C. and the phases separated. A 30% aqueous solution of sodium hydroxide was then added to the organic layer and the mixture warmed up to reflux for 2 h until 2-Chloro-1-(6-fluoro-1-benzopyran-2-yl)-ethanol had disappeared. The biphasic mixture was cooled to 20-25° C., the phases separated. The organic layer was washed with water (5 ml) and concentrated until dryness to give 6-Fluoro-2-oxiranyl-1-benzopyran as a mixture of the 4 diastereoisomers [(R,S);(S,R):(R,R);(S,S)]=52:48 (1.7 g, 91% yield).

Provenance & Evidence