Lithium hydroxide, monohydrate → Tesaglitazar

Participants

Reaction Conditions

Reaction Steps

Lithium hydroxide hydrate (0.229 g; 5.45 mmole) dissolved in water (6 ml) was slowly added to a mixture of (S)-2-ethoxy-3-[4-(2-{4-methanesulfonyloxyphenyl} ethoxy)phenyl]-propanoic acid ethyl ester (2.29 g; 5.24 mmole) in tetrahydrofuran (50 ml) and water (10 ml) at 5° C. The reaction mixture was stirred at 5° C. for 2.5 hours, at 20° C. for 3 hours, at 0° C. for 15 hours and at 20° C. for 3,5 hours. More lithium hydroxide hydrate (44 mg, 1.05 mmole) dissolved in water (1 ml) was added at 10° C. After another 21.5 hours of stirring at 10° C., more lithium hydroxide hydrate (44 mg; 1.05 mmole) dissolved in water (1 ml) was added. The reaction mixture was stirred at 25° C. for 3 hours and then kept at 2° C. for 67 hours. Tetrahydrofuran was evaporated in vacuo and then water and ethyl acetate were added. Insoluble material was filtered off and the phases of the filtrate were separated. The water phase was washed twice with ethyl acetate, acidified with hydrochloric acid (2 M; 3.2 ml) and extracted with ethyl acetate (30 ml). The organic phase was washed twice with water, dried (magnesium sulfate), filtered and the solvent was evaporated in vacuo to give 1.9 g (yield 72% in 2 steps) of (S)-2-ethoxy-3-[4-(2-{4-methanesulfonyloxyphenyl}-ethoxy)phenyl]propanoic acid.

Provenance & Evidence