Acetic Acid → methyl 2-(4-(benzyloxy)phenyl)-4-oxobutanoate

Participants

Reaction Conditions

Reaction Steps

Under a nitrogen atmosphere, 2-(4-benzyloxy-phenyl)-pent-4-enoic acid methyl ester (750 g; 2.53 mol) is dissolved in ethyl acetate (7.5 L), and the resulting mixture cooled to −70° C. Ozone is introduced subsurface into the reaction for 3 h causing the reaction mixture to turn blue. The reaction mass is purged subsurface with nitrogen for 0.5 h to displace any residual ozone. At this point HPLC analysis indicates complete consumption of the starting material. The reaction mixture is warmed to −30° C. and held. In a separate vessel, zinc (450 g; 6.88 mol) and aqueous acetic acid (500 mL in 500 mL water) are combined and cooled to 0° C. The contents of the ozonolysis reactor are added to the aqueous acidic zinc mixture at such a rate as to maintain a reaction temperature of ≦0° C. After the addition is complete and the mixture has been held for 2 h, HPLC indicates conversion of intermediates to the desired aldehyde. The reaction mixture is filtered through Celite®, washed with water (2×4.5 L), and water (4.5 L) is added to the organic phase. Sodium bicarbonate (150 g; 1.79 mol) is added to the mixture, and stirring for 0.25 h gives a pH of >7. The aqueous layer is removed, and the volume is reduced to 2.25 L by reduced pressure distillation. The mixture is held at 50° C., and heptane (3L) is added to slowly provide a precipitate. The resulting slurry is cooled to 20° C. over 2 h, the solids are filtered, washed with heptane (3 L), and dried to constant weight at 45° C. and ˜25″ Hg. The title aldehyde, compound A (513 g; 68% isolated yield) is afforded as a tan solid.

Provenance & Evidence