反应详情

温度

42.5 °C

Under nitrogen, chlorotrimethyl silane (28.0 g) was added to a slurry of (S)-α-amino-1,3-dioxolane-2-pentanoic acid (20.9 g) and dimethyl sulfite (12.0 g) in methanol (240 ml) to afford a homogeneous solution. Following the observation of an exotherm to 29° C. , the solution was heated to 40-45° C. , stirred at that temperature for 8 hours and at about 22° C. for up to 72 hours. In-process HPLC analysis showed that the reaction was complete (about 93 M% conversion to product) and the resulting solution was cooled to −5 to −10° C. With stirring, the apparent pH of the mixture was adjusted to 11.7 to 11.9 by the slow careful addition of 32% (or 4.45 M) methanolic potassium methoxide solution (70 ml) maintaining the temperature in the range of −5 to 0° C. Analysis of the product slurry (1H-NMR) indicated that the neutralizaiton was complete. The solvent of the product slurry was exchanged with ethyl acetate by first concentrating the thin slurry under vacuum at less than 30° C. to 300 ml volume followed by the addition of ethyl acetate until the removal of methanol was completed as judged by in-process GC analysis (less than 1 AP). Upon completion of the solvent exchange, the batch volume was adjusted to about 400 ml with ethyl acetate and the resulting slurry was filtered. Poly(acrylic acid co-acrylamide), potassium salt (3.0 to 3.2 g) and water (30-32 ml) were added to the filtrate. The mixture was stirred for about 35 minutes and filtered, optionally, the poly (acrylic acid co-acrylamide), potassium salt treatment can be repeated on the filtrate if the quantity of ethylene glycol exceeds 0.15 equivalents, as judged by in-process GC analysis. Following in-process HPLC analysis, 17.4 g of the title product was obtained as an ethyl acetate solution in 80.8 M% yield.

1. customto afford a homogeneous solution
2. customto 29° C.
3. temperaturethe resulting solution was cooled to −5 to −10° C
4. stirringWith stirring
5. temperaturemaintaining the temperature in the range of −5 to 0° C
6. concentrationby first concentrating the thin slurry under vacuum at less than 30° C. to 300 ml volume
7. additionfollowed by the addition of ethyl acetate until the removal of methanol
8. filtrationthe resulting slurry was filtered
9. additionPoly(acrylic acid co-acrylamide), potassium salt (3.0 to 3.2 g) and water (30-32 ml) were added to the filtrate
10. stirringThe mixture was stirred for about 35 minutes
11. filtrationfiltered