4829-14-5

32315-10-9

302-72-7

2224-52-4

To a 100 L glass reactor was added ethyl acetate (37 L, moisture content <0.01%), and DL-alanine (500 g, particle size <200 μm, moisture content <0.01%) that had been powdered and vacuum dried. The outlet of the reactor was connected to a scrubber containing 10% sodium hydroxide solution and an inert atmosphere was established by passing nitrogen. Triphosgene (500 g) was dissolved in ethyl acetate (5 L) and transferred to a charging tank. The reaction mixture was heated to 70-80°C, followed by slow dropwise addition of the triphosgene solution over a period of 4-6 hours. Upon addition of about 4.2 L of triphosgene solution, the reaction mixture became clarified. The addition of the remaining triphosgene solution was continued and the reaction was maintained at 70-80 °C for 1 hour. Upon completion of the reaction, the mixture was cooled to 60 °C and filtered through a hyflow bed under nitrogen protection. The filtrate was transferred back to the reactor, concentrated to 1/3 of the original volume, hexane (30 L, moisture content <0.01%) was added and stirred at 0-5 °C for 1 h to promote crystallization. The crystallized product was collected by filtration, dried under nitrogen atmosphere and stored at -20 °C. The product (S)-4-methyloxazolidine-2,5-dione was obtained as 500g in 87.7% yield, 99.7% purity (determined by non-aqueous titration), 0.01% chloride content (determined by silver measurement), and <0.01% free alanine content (determined by thin layer chromatography).