Citric Acid → (R)-3-(4-Methoxybenzyl)-4-acetylthiazolidin-2-one

Participants

Reaction Conditions

Reaction Steps

A dry three-necked round bottom flask fitted with an internal temperature probe and a mechanical stirrer was charged with a solution of methylmagnesium chloride in THF (0.805 L, 3 M). The solution was purged with nitrogen and cooled to 0° C. In a separate flask, the title compound from Example 4 (250.0 g, 0.805 mol) was dissolved in dry THF (1.0 L). This solution was added to the solution of methylmagnesium chloride at a rate that maintained an internal reaction temperature less than 5° C. The reaction was monitored by HPLC and was complete upon the disappearance of the starting material (approx. 20 minutes after completing the addition). The reaction mixture was slowly added into a 10% citric acid solution (1 L) at a rate that maintained a temperature of less than 25° C. The mixture was diluted with water, and the THF was removed by distillation at 70° C. (80° C. external) and 1 atm. The product was extracted with ethyl acetate, and the organic phase was separated and concentrated by distillation at 76° C. (95° C. external) and 1 atm to a final volume of ˜800 mL. The solution was allowed to cool to room temperature, and n-heptane was added to give a precipitate. The suspension was stirred for 30 minutes, and the solid was isolated by filtration and dried in a vacuum oven at 40° C. overnight to afford the title compound (170 g, 80%).

Provenance & Evidence