反应详情

温度

42 °C

Under nitrogen, chlorotrimethyl silane (532 g) was added to a slurry of (S)-α-amino-1,3-dioxolane-2-pentanoic acid (380 g) and dimethyl sulfite (228 g) in methanol (4560 ml) to afford a homogeneous solution. Following the observation of an exotherm to 29° C., the solution was heated to 42° C., stirred at that temperature for 8 hours at about 22° C. for 16 hours. In process HPLC analysis showed that a 93 M % yield of product was obtained. A portion of the resulting solution containing 53.4 g of title product was cooled to -5 to -10 °C. with stirring and the apparent pH of the mixture was adjusted from -0.38 to about 8.32 by the slow careful addition of 32% methanolic potassium methoxide solution (2×100 ml). The pH of the mixture was further adjusted to 11.45 by the careful addition of potassium methoxide (16 ml) maintaining the temperature below 5° C. In process 1H NMR analysis of the product slurry indicated that the neutralization was complete. The solvent of the product slurry was exchanged with ethyl acetate (total 3160 ml) via a vacuum distillation at less than 30° C., concentrated to 400 ml volume, diluted with tert-butyl methyl ether (800 ml), cooled to 0° C., agitated for 30 minutes, and filtered. The filtrate was treated with calcium chloride dihydrate (135 g in 9 portions) until in-process GC assay indicated that ethylene glycol was absorbed by the calcium chloride dihydrate. The resulting slurry was filtered to afford a filtrate containing 49.7 g of title product.

1. customto afford a homogeneous solution
2. customto 29° C.
3. customwas obtained