Hydrochloric Acid → Clobuzarit

Participants

Reaction Steps

A solution of 4-(4-chlorophenyl)benzaldehyde (41.5 g.) in chlorobenzene (250 ml.) containing in addition 2-hydroxy-2-methylpropionic acid (29.7 g.) and p-toluenesulphonic acid monohydrate (2.7 g.) was heated under reflux for 6 hours at reduced pressure (105° C., 313 mm Hg) with continuous removal of water by azeotropic distillation. The solution was then cooled, washed successively with 10% w/v sodium carbonate solution (500 ml.) and water (2×500 ml.), dried (MgSO4), filtered and diluted with fresh chlorobenzene to a volume of 350 ml. to give a solution containing 14.3% w/v of 2-[4-(4-chlorophenyl)-phenyl]-5,5-dimethyl-1,3-dioxolanone-4-one, as estimated by gas-liquid chromatography. This solution (35 ml.) was added during 1 hour at 0° to 5° C. under an argon atmosphere to a stirred solution of t-butyl magnesium chloride [prepared from magnesium turnings (1.61 g.) and a solution of t-butyl chloride (9.33 ml.) in anhydrous ether (40 ml.)]. The mixture was stirred for 1 hour at 0° to 5° C. and then for a further 16 hours at room temperature before being poured into 1.5 M hydrochloric acid (100 ml.). The organic phase was separated and washed with water (2×100 ml.), dried (Na2SO4) and evaporated to give 2-[4-(4-chlorophenyl)benzyloxy]-2-methyl-propionic acid (9.23 g.), m.p. 154°-155° C., after recrystallisation from toluene.

Provenance & Evidence