BrCCl.[CH3:4][O:5][C:6]([CH:8]1[CH:13]=[CH:12][C:11]2[CH:14]=[C:15]([F:18])[CH:16]=[CH:17][C:10]=2[O:9]1)=O.[Li]CCCC.CCCCCC>C1COCC1.O>[F:18][C:15]1[CH:16]=[CH:17][C:10]2[O:9][CH:8]([CH:6]3[CH2:4][O:5]3)[CH:13]=[CH:12][C:11]=2[CH:14]=1
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).
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