反应详情

温度

41 °C

(S)-α-Amino-1,3-dioxolane-2-pentanoic acid (100 g), methanol (1200 ml) and dimethyl sulfite (44.8 ml) were charged to a 250 ml, three neck flask equipped with a mechanical agitator, thermocouple, heating mantle, condenser, nitrogen inlet, and vent. Chlorotrimethylsilane (168 ml) was added to the resulting slurry and the reaction mixture was heated at 40 to 42° C. for about 8 hours, followed by stirring at ambient temperature for 8 hours to afford a solution of (S)-2-amino-6,6-dimethoxyhexanoic acid, methyl ester, hydrochloride salt. Potassium bicarbonate (208.6 g) was slurried in methanol (400 ml) contained in a 5 liter three neck flask and the reaction containing the hydrochloride salt of (S)-2-amino-6,6-dimethoxyhexanoic acid, methyl ester was neutralized by adding it to the potassium bicarbonate slurry slowly over 1.5 hours while maintaining the pH of the mixture above 6.9. The solvent of the resulting slurry was replaced with n-butyl acetate by vacuum distillation (50 to 60 mm Hg and 30 to 40° C.) maintaining a pot volume of about 2 liters. After 2.25 liters of n-butyl acetate were distilled, methanol (1.25 1) was added to the distillation vessel and the distillation was continued, maintaining a pot volume of not less than 2 liters, until the water content of the slurry supernatant was less than 0.05 weight percent and the methanol level was less than 5 relative area percent by gas chromatography. Hexane (1.5 1) was charged to the resulting slurry and it was then cooled to -5° C. After stirring the mixture for 1 hours it was filtered and the filter-cake was washed with hexane (2×100 ml). The resulting hazy filtrate was polish filtered to afford a clear filtrate. The clear filtrate was warmed to 20 to 25° and a methanolic (1333 ml) solution of oxalic acid dihydrate (33.3 g) was added slowly over about 2 hours. The resulting slurry of (S)-2-amino-6,6-dimethoxy-hexanoic acid, methyl ester, oxalic acid salt (2:1) was agitated for 18 hours at ambient temperature and the product was collected on a filter. The product wet-cake was washed with acetonitrile (4×100 ml) and dried under vacuum at 45° C. to afford 103.2 g of the desired product.

1. customequipped with a mechanical agitator
2. temperaturethermocouple, heating mantle, condenser, nitrogen inlet, and vent