Water → Tesaglitazar

Participants

Reaction Steps

To the oil of ethyl (S)-2-ethoxy-3-[4(2-{4-methanesulfonyloxyphenyl}ethoxy)phenyl]propanoate (723 g (71.2% assay), 1.18 mol. 1.0 eq) was added THF (3900 ml). When a homogenous solution was formed, water (900 ml) was added. The mixture was cooled to +10° C. Lithium hydroxide solution (390 ml, 4 M, 1.32 eq) was added over 1 hour. The temperature was then raised to +30° C. and the reaction allowed to proceed at this temperature for 2-3 hours. The reaction was stopped when the conversion was >99%. EtOAc (500 ml) was added and the mixture cooled to room temperature. The solution was stirred for about 30 minutes and the THF was evaporated off. When about 80-90% of the THF was evaporated, water (1900 ml) was added. The evaporation was continued until no THF remained in the mixture. The alkaline water solution was then washed with EtOAc (1000 ml, 2×1250 ml, and 950 ml). The pH of the water solution of (S)-2-ethoxy-3-[4(2-{4-methanesulfonyloxyphenyl}ethoxy)phenyl]propanoic acid was then adjusted to 2.0-2.5 with HCl (aq) (550 ml, 3.0 M). EtOAc (2500 ml) was added and the phases separated. The ethyl acetate solution of (S)-2-ethoxy-3-[4-(2-{4-methanesulfonyloxyphenyl}ethoxy)phenyl]propanoic acid was then washed with water (700 ml) and after separation evaporated to dryness. The remaining oil was then used in the following crystallisation.

Provenance & Evidence