Acetic Acid → (e)-11-(Bromomethylene)-3-fluoro-6,11-dihydrodibenzo[b,e]oxepine

Participants

Reaction Conditions

Reaction Steps

To a clean, dry 100-gallon reactor with stirring under nitrogen, charge isopropanol (125 L), (E)-(3-fluoro-6H-dibenzo[b,e]oxepin-11-ylidene)-acetic acid ethyl ester (13.857 kg, 46.42 mol), and a solution of lithium hydroxide (3.896 kg, 92.84 mol) in water (54 L). Heat the reaction mixture to 80° C. and stir for 2 h. Cool the reaction mixture to 40° C. and add acetic acid (5.575 kg, 92.84 mol) over 20 min between 40° C. and 45° C. Add N-bromosuccinimide (48.74 mol, 8.676 kg) portion-wise over 30 min at <45° C. Cool the reaction to room temperature and stir for a minimum of 12 h. Add an aqueous solution of sodium bisulfite (−37.7 L) and stir 15 min. Add an aqueous solution of sodium bicarbonate (−37.7 L) and stir 15 min. Add water (129 L) and stir 30 min. Filter to collect the resulting solids, washing with isopropanol:water (1:1, 2×20 L). Dry the solids under vacuum at 32° C. to a constant weight to obtain the title compound (13.8 kg, 97%).

Provenance & Evidence