Trifluoroacetic acid → 7-bromo-4-fluoro-2-methoxy-9H-xanthen-9-one

Participants

Reaction Conditions

Reaction Steps

A dry 100 L glass jacketed reactor equipped with an addition funnel, reflux condenser and temperature probe was charged with 5-bromo-2-(2-fluoro-4-methoxyphenoxy)benzoic acid (2340 g, 6.9 mol). TFA (11.7 L) was carefully added to the mixture followed by TFAA (1144 mL). Boron trifluoride diethyl etherate (85 mL, 0.68 mol) was then carefully added, and the mixture was stirred for 4 hours at which point the reaction was transferred to another 100 L glass reactor containing 35.1 L of water cooled at 0° C. The resulting slurry was allowed to warm to RT and stirred for 1 hour. The solids were filtered and washed with water (4.7 L) and 3 N NaOH (2×3.5 L) and water (7 L). The solids were transferred into a 22 L reactor and acetone (4.7 L) was added. The solids were slurried for 1.5 hour and the filtered, washing well with acetone (4.7 L). An additional slurry with acetone (6.4 L @ 45° C.) provided 1310 g of 7-bromo-4-fluoro-2-methoxy-9H-xanthen-9-one as an off white solid.

Provenance & Evidence