Hatco Chemical Corporation

Mary S Chen

K Ming Wan

Clay T Chen

Anil D Pendse

N-Benzyloxycarbonyl-L-aspartic acid (Z-Asp) crystals several times larger than those obtained by conventional crystallization are prepared by acidifying an alkaline aqueous solution of a metal salt of Z-Asp at high temperatures of between about 20.degree. to 45.degree. C. The resulting large crystals contain less moisture and less impurities such as sodium chloride, dipeptide and benzyl alcohol, etc. than those crystals obtained at lower temperatures and they are easily processed for preparing aspartame.

Preparation of large crystals of N-benzyloxycarbonyl-L-aspartic acid

N-Benzyloxycarbonyl-L-aspartic acid (Z-Asp) is synthesized by adding benzyl chloroformate to a solution of L-aspartic acid and sodium hydroxide at relatively high temperatures of 35.degree.-55.degree. C. and over a wide pH range of 9.2-12.0 and acidifying the sodium salt product. The Z-Asp is prepared in high yields exceeding 90% and purity of better than 99% with only a minor amount of the by-product N-benzyloxycarbonyl aspartyl aspartic acid. The Z-Asp is suitable for conversion to aspartame. Carrying out the reaction at high temperatures significantly reduces cycle time while maintaining a high yield with a low dipeptide and unreacted L-aspartic acid content.

Synthesis of N-benzyloxycarbonyl-L-aspartic acid

N-Benzyloxycarbonyl-L-aspartic acid (Z-Asp) is synthesized by adding benzyl chloroformate to a solution of L-aspartic acid and sodium hydroxide at temperatures from about 5.degree.-55.degree. C. and over a wide pH range of about 9.2 to 13.8 in the presence of a surfactant and/or a buffer and then acidifying the reaction mixture. Carrying out the reaction in the presence of a surfactant reduces cycle time, while maintaining a high yield with low by-product content. The buffer prevents wide fluctuations in pH and minimizes localized reaction. These conditions are desirable when the reaction rate has been increased by addition of a surfactant or an increase in temperature of the reaction mixture.

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Edison, NJ, United States of America

Mary S Chen