Hydrochloric Acid → 3-(4-(5-Bromo-2-chlorobenzyl)phenoxy)oxetane

Participants

Reaction Conditions

Reaction Steps

To a solution of crude 4-(5-bromo-2-chlorobenzyl)phenol (3.0 g, 10 mmol) and cesium carbonate (4.9 g, 15 mmol) in N,N-dimethylformamide (77.5 mL) at room temperature was added a solution of toluene-4-sulfonic acid oxetan-3-yl ester (3.5 g, 15 mmol) in N,N-dimethylformamide (8 mL). The mixture was heated to 65° C. for 22 hours whereupon an additional aliquot of cesium carbonate (3.3 g, 10 mmol) was added. The reaction mixture was stirred for a further 12 hours at 120° C., cooled to room temperature whereupon water and ethyl acetate were added and the mixture was carefully acidified with 1N aqueous hydrochloric acid solution. The organic layer was separated, washed with brine (3 times), and concentrated in vacuo. Purification via Biotage MPLC (silica gel, eluting with a gradient of 0 to 25% ethyl acetate in heptane) afforded 3-(4-(5-bromo-2-chlorobenzyl)phenoxy)oxetane (2.5 g, 70% yield) as a white solid.

Provenance & Evidence