Ajinomoto Co., Ltd.

Shinichi Kishimoto

Hideo Takeda

Masayoshi Naruse

Haruo Kawasaki

Masao Nakamura

Toshihisa Kato

Harutoshi Oura

Takehiko Kataoka

Tadashi Takemoto

Akihiko Yasaki

Sou Abe

So Abe

Katsumi Sugiyama

Chikahiko Eguchi

Yoichi Ozawa

Harutoshi Ohura

Emiko Shinohara

Osahiro Sato

Toru Ikeda

Toshihide Yukawa

Satoshi Kumon

Atsuhiko Hirano

Yoshinobu Uchida

Mikiya Kano

Kimiyasu Sakamoto

Toshiaki Tsuji

Satoshi Yamahara

A crystalline L-alpha-aspartyl-L-phenyl-alanine methyl ester product is disclosed. The product is obtained by crystallizing the ester from an aqueous solution, by cooling. The initial concentration of ester in the aqueous solution used provides at least 10 grams of precipitated solid phase per liter of solution. The solution is cooled through conductive heat transfer without effecting forced flow to form a sherbet-like pseudo solid phase.

Process for crystallizing L-.alpha.-aspartyl-L-phenylanlanine methyl

A method for dissolving crystalline L-alpha-aspartyl-L-phenyl alanine methyl ester product is disclosed. The product is obtained by crystallizing the ester from an aqueous solution, by cooling. The initial concentration of ester in the aqueous solution used provides at least 10 grams of precipitated solid phase per liter of solution. The solution is cooled through conductive heat transfer without effecting forced flow to form a sherbet-like pseudo solid phase

Method of dissolving crystals of L-.alpha.-aspartyl-L-phenyl alanine

A crystalline L-.alpha.-aspartyl-L-phenylalanine methyl ester product and the process for obtaining the same are disclosed. This product is obtained by adjusting the initial concentration of L-.alpha.-aspartyl-L-phenylalanine methyl ester in an aqueous solution so that the amount of precipitated solid, formed after cooling said solution, is about 10 grams or more of precipitate per liter of solvent. The solution is then cooled through conductive heat transfer, without causing forced flow, to obtain a sherbet-like pseudo solid phase.

Process for crystallizing L-.alpha.-aspartyl-L-phenylalanine methyl ester

Wet crystals of .alpha.-L-aspartyl-L-phenylalanine methyl ester with low water content can be obtained with high efficiency by solid-liquid separation of an aqueous suspension of .alpha.-L-aspartyl-L-phenylalanine methyl ester. The aqueous suspension is compressed at a final pressure of at least 20 kg/cm.sup.2 as a bearing pressure, and the wet crystals are dried after compression.

Process for producing .alpha.-L-aspartyl-L-phenylalanine methyl ester

The present invention provides an industrial method of producing N-formyl-L-aspartic anhydride from N-formyl-L-aspartic acid, formic acid and acetic anhydride with less residual formic acid than conventional methods.

Method of preparing N-formyl-L-aspartic anhydride

A method for dissolving crystalline L-alpha-aspartyl-L-phenyl-alanine methyl ester product is disclosed. The product is obtained by crystallizing the ester from an aqueous solution, by cooling. The initial concentration of ester in the aqueous solution used provides at least 10 grams of precipitated solid phase per liter of solution. The solution is cooled through conductive heat transfer without effecting forced flow to form a sherbet-like pseudo solid phase.

Method of dissolving crystals of L-.alpha.-aspartyl-L-phenylalanine

A process for obtaining dry crystals of .alpha.-L-aspartyl-L-phenylalanine methyl ester having a water content of about 2 wt. % to about 6 wt. % based on the weight of the wet crystals is disclosed. This process comprises exposing wet crystals of .alpha.-L-aspartyl-L-phenylalanine methyl ester, having a water content not greater than 50 wt. % based on the weight of the wet crystals and obtained by the crystallization of .alpha.-L-aspartyl-L-phenylalanine methyl ester from an unagitated solution of .alpha.-L-aspartyl-L-phenylalanine methyl ester, to a flow of air having a temperature of 80.degree. C. to 200.degree. C.

Process for preparing dry crystals of the methyl ester of

A process for quickly and reproducibly obtaining .alpha.-L-aspartyl-L-phenylalanine methyl ester with controlled water content is disclosed. Wet crystals of .alpha.-L-aspartyl-L-phenylalanine methyl ester obtained by crystallization are subjected to a drying step to adjust the water content to not more than 5 wt %, and subsequently a gas adjusted to a temperature of 20-80.degree. C. and relative humidity of 20-90 RH % is contacted with the dried crystals to control water content.

The problems in crystallization of .alpha.-L-aspartyl-L-phenylalanine methyl ester, namely, problems in crystal slurry properties in solid-liquid separation, scaling at heat transfer surfaces, and the like, are solved by a method for crystallization of .alpha.-L-aspartyl-L-phenylalanine methyl ester which comprises cooling a solution of .alpha.-L-aspartyl-L-phenylalanine methyl ester by indirect heat exchange with a coolant while stirring, wherein the solution is cooled by circulating a coolant while continuously adding an aqueous solution of .alpha.-L-aspartyl-L-phenylalanine methyl ester dropwise to a crystallizing solution of .alpha.-L-aspartyl-L-phenylalanine methyl ester having a temperature difference of not greater than 20.degree. C. from the coolant, thereby to keep a temperature difference of not greater than 20.degree. C. between the coolant and the crystallizing solution.

Method for crystallization of .alpha.-L-aspartyl-L-phenylalanine methyl

Granules of .alpha.-L-aspartyl-L-phenylalanine methyl ester, containing IB crystals of the ester and having a grain size of from 100 to 1400 .mu.m have improved water solubility.

Granules of .alpha.-L-aspartyl-L-phenylalanine methyl ester

A method for the solid-liquid separation of a suspension of .alpha.-L-aspartyl-L-phenylalanine methyl ester (.alpha.-APM) or its hydrochloride salt (.alpha.-APM.HCl), wherein an aqueous suspension of .alpha.-L-aspartyl-L-phenylalanine methyl ester or its hydrochloride salt is subjected to continuous separation by vacuum filtration.

Method of preparing .alpha.-L-aspartyl-L-phenylalanine methyl ester or

In crystallizing .alpha.-APM from a water solution or a mixed solvent solution of water and a lower alcohol in a crystallizer, the pressure in the crystallizer is held at not higher than atmospheric pressure, a water or water/alcohol mixed solution of .alpha.-APM is fed into the crystallizer with stirring so that the solvent is vaporized, and the crystallization solution is cooled and crystallized by the latent heat of vaporization or is heated so as to prevent supercooling.

Method of crystallizing .alpha.-L-aspartyl-L-phenylalanine methyl ester

A method for the recovery of .alpha.-L-aspartyl-L-phenylalanine methyl ester, L-phenylalanine and L-aspartic acid from the mother liquor obtained by the solid-liquid separation of a suspension of .alpha.-L-aspartyl-L-phenylalanine methyl ester crystals is disclosed.

Method for recovery of .alpha.-L-aspartyl-L-phenylalanine methyl ester,

A method of preparing .varies.-L-aspartyl-L-phenylalanine methyl ester hydrochloride (.varies.-APM.HCL) from a reaction mixture of N-formyl-L-aspartic acid anhydride and L-phenylalanine methyl ester (PM), wherein .alpha.-APM.HCl is produced without isolating an intermediate by solid-liquid separation during the course of the reaction process.

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Kawasaki, Japan

Shinichi Kishimoto