JPH01290655A - Production of amino acid methyl ester mineral acid salt - Google Patents
Production of amino acid methyl ester mineral acid saltInfo
- Publication number
- JPH01290655A JPH01290655A JP11937488A JP11937488A JPH01290655A JP H01290655 A JPH01290655 A JP H01290655A JP 11937488 A JP11937488 A JP 11937488A JP 11937488 A JP11937488 A JP 11937488A JP H01290655 A JPH01290655 A JP H01290655A
- Authority
- JP
- Japan
- Prior art keywords
- methanol
- amino acid
- methyl ester
- added
- acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000002253 acid Substances 0.000 title claims abstract description 16
- 229910052500 inorganic mineral Inorganic materials 0.000 title claims abstract description 14
- 239000011707 mineral Substances 0.000 title claims abstract description 14
- 150000003839 salts Chemical class 0.000 title claims abstract description 9
- -1 amino acid methyl ester Chemical class 0.000 title claims abstract description 8
- 238000004519 manufacturing process Methods 0.000 title claims description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 117
- 150000001413 amino acids Chemical class 0.000 claims abstract description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000003960 organic solvent Substances 0.000 claims abstract description 9
- 230000018044 dehydration Effects 0.000 claims abstract description 8
- 238000006297 dehydration reaction Methods 0.000 claims abstract description 8
- 238000000034 method Methods 0.000 claims description 13
- 238000005886 esterification reaction Methods 0.000 claims description 9
- 150000004702 methyl esters Chemical class 0.000 claims description 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 abstract description 63
- 238000006243 chemical reaction Methods 0.000 abstract description 23
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 abstract description 8
- 239000002994 raw material Substances 0.000 abstract description 7
- 239000000203 mixture Substances 0.000 abstract description 4
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 abstract description 3
- 108010011485 Aspartame Proteins 0.000 abstract description 2
- 239000000605 aspartame Substances 0.000 abstract description 2
- 229960003438 aspartame Drugs 0.000 abstract description 2
- 235000010357 aspartame Nutrition 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 238000010992 reflux Methods 0.000 abstract description 2
- 150000001875 compounds Chemical class 0.000 abstract 1
- 235000003599 food sweetener Nutrition 0.000 abstract 1
- 238000010438 heat treatment Methods 0.000 abstract 1
- 108090000765 processed proteins & peptides Proteins 0.000 abstract 1
- 102000004196 processed proteins & peptides Human genes 0.000 abstract 1
- 239000003765 sweetening agent Substances 0.000 abstract 1
- 239000013078 crystal Substances 0.000 description 26
- 229940024606 amino acid Drugs 0.000 description 17
- 235000001014 amino acid Nutrition 0.000 description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- 238000004128 high performance liquid chromatography Methods 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 238000004458 analytical method Methods 0.000 description 11
- 238000000921 elemental analysis Methods 0.000 description 10
- 238000001035 drying Methods 0.000 description 8
- 239000002002 slurry Substances 0.000 description 7
- 229960003767 alanine Drugs 0.000 description 6
- 229960005261 aspartic acid Drugs 0.000 description 6
- 230000032050 esterification Effects 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 5
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 238000006460 hydrolysis reaction Methods 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 229960001153 serine Drugs 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 3
- CKLJMWTZIZZHCS-UWTATZPHSA-N L-Aspartic acid Natural products OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 description 3
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- QNAYBMKLOCPYGJ-UWTATZPHSA-N L-Alanine Natural products C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 229960003646 lysine Drugs 0.000 description 2
- 235000018977 lysine Nutrition 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 229960005190 phenylalanine Drugs 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
- YKMJOAVCSAOXOU-UHFFFAOYSA-N 2-phenyl-7h-purin-6-amine Chemical compound N=1C=2N=CNC=2C(N)=NC=1C1=CC=CC=C1 YKMJOAVCSAOXOU-UHFFFAOYSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- BVHLGVCQOALMSV-JEDNCBNOSA-N L-lysine hydrochloride Chemical compound Cl.NCCCC[C@H](N)C(O)=O BVHLGVCQOALMSV-JEDNCBNOSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- RJUFJBKOKNCXHH-UHFFFAOYSA-N Methyl propionate Chemical compound CCC(=O)OC RJUFJBKOKNCXHH-UHFFFAOYSA-N 0.000 description 1
- PSFABYLDRXJYID-VKHMYHEASA-N N-Methylserine Chemical compound CN[C@@H](CO)C(O)=O PSFABYLDRXJYID-VKHMYHEASA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- BYHXBBOSJKPUJL-BYPYZUCNSA-N dimethyl (2s)-2-aminobutanedioate Chemical compound COC(=O)C[C@H](N)C(=O)OC BYHXBBOSJKPUJL-BYPYZUCNSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- DWKPPFQULDPWHX-VKHMYHEASA-N l-alanyl ester Chemical compound COC(=O)[C@H](C)N DWKPPFQULDPWHX-VKHMYHEASA-N 0.000 description 1
- 229960003136 leucine Drugs 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- NDBQJIBNNUJNHA-DFWYDOINSA-N methyl (2s)-2-amino-3-hydroxypropanoate;hydrochloride Chemical compound Cl.COC(=O)[C@@H](N)CO NDBQJIBNNUJNHA-DFWYDOINSA-N 0.000 description 1
- SWVMLNPDTIFDDY-FVGYRXGTSA-N methyl (2s)-2-amino-3-phenylpropanoate;hydrochloride Chemical compound Cl.COC(=O)[C@@H](N)CC1=CC=CC=C1 SWVMLNPDTIFDDY-FVGYRXGTSA-N 0.000 description 1
- IYUKFAFDFHZKPI-DFWYDOINSA-N methyl (2s)-2-aminopropanoate;hydrochloride Chemical compound Cl.COC(=O)[C@H](C)N IYUKFAFDFHZKPI-DFWYDOINSA-N 0.000 description 1
- KPNBUPJZFJCCIQ-LURJTMIESA-N methyl L-lysinate Chemical compound COC(=O)[C@@H](N)CCCCN KPNBUPJZFJCCIQ-LURJTMIESA-N 0.000 description 1
- 229940017219 methyl propionate Drugs 0.000 description 1
- 229940078547 methylserine Drugs 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 229960004295 valine Drugs 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【発明の詳細な説明】
Ｃ産業上の利用分野］
本発明は、アミノ酸メチルエステル鉱酸塩を効率よく、
かつ高収率で製造する方法に関するものである。[Detailed Description of the Invention] C. Industrial Application Field] The present invention provides efficient processing of amino acid methyl ester mineral salts.
The present invention also relates to a method for producing the same with high yield.
本発明のアミノ酸メチルエステル鉱酸塩は、ペプチド合
成の中間体として重要であり、また、ジペプチド系の甘
味料アスパルテームの合成原料、あるいは医薬原料とし
て有用なものである。The amino acid methyl ester mineral acid salt of the present invention is important as an intermediate for peptide synthesis, and is also useful as a raw material for the synthesis of the dipeptide sweetener aspartame or as a raw material for pharmaceuticals.
アミノ酸のエステル化法は古くから知られており、基本
的には１８８８年にＣｕｔｔｔｕｓ等が開発した方法が
今日も用いられている。この方法は、アミノ酸を懸濁し
たアルコールに塩化水素を飽和させ、反応した後過剰の
アルコールを除き、さらに反応に用いたアルコールを添
加して濃縮することを繰り返し、エーテルや石油エーテ
ルを用いて結晶化することにより、目的物を得るもので
ある。しかし、この方法では、大量のアルコールを用い
る必要がある上に、回収したアルコールが水を含んでい
るために、そのままでは再使用できない、また、用いる
アルフールがメタノールのように水と共沸しないもので
あると、反応後過剰のアルコールを除いたあとに水が残
り、ｖＡｗｉを操り返す過程でエステルの加水分解が進
行する。このために、濾過、乾燥で得られるエステル化
物の収率は高々９０％程度である。さらに、得られたエ
ステルに加水分解で生成した原料アミノ酸が多量に含ま
れる場合には、これらの不純物からの分離が困難である
という問題も生じる。The esterification method of amino acids has been known for a long time, and basically the method developed by Cuttus et al. in 1888 is still used today. In this method, hydrogen chloride is saturated in alcohol in which amino acids are suspended, and after the reaction, excess alcohol is removed, and the alcohol used in the reaction is added and concentrated repeatedly, followed by crystallization using ether or petroleum ether. The object is obtained by converting it into something. However, this method requires the use of a large amount of alcohol, and since the recovered alcohol contains water, it cannot be reused as it is, and the alcohol used is not azeotropic with water, like methanol. In this case, after the excess alcohol is removed after the reaction, water remains, and the hydrolysis of the ester progresses during the process of re-manipulating vAwi. For this reason, the yield of the esterified product obtained by filtration and drying is about 90% at most. Furthermore, when the obtained ester contains a large amount of raw material amino acids produced by hydrolysis, there arises the problem that separation from these impurities is difficult.
また、結晶化にエーテル類を用いるため、それらの取扱
や回収上の問題から、工業的な実施は困難である。Furthermore, since ethers are used for crystallization, industrial implementation is difficult due to problems in handling and recovering them.
他にも、アミノ酸をＰ−）ルエンスルホン酸、エタノー
ルおよび四塩化炭素と加熱して、生成する水を共沸混合
物として系外に除き、アミノ酸エチルエステルのＰ−）
ルエンスルホン酸塩として得る方法（日化誌８３．１１
５１．１９６２年）も知られているが、不揮発性の酸を
用いる必要があることや、メタノールの場合には共沸に
よりアルコールが系外に除かれるため、大量のメタノー
ルを使用する必要があるなど、工業的には問題があった
。In addition, amino acids are heated with P-) luenesulfonic acid, ethanol, and carbon tetrachloride, and the resulting water is removed from the system as an azeotrope to produce P-) amino acid ethyl esters.
Method for obtaining luenesulfonate (Nikkashu 83.11
51.1962) is also known, but it requires the use of a nonvolatile acid, and in the case of methanol, the alcohol is removed from the system by azeotropy, so it is necessary to use a large amount of methanol. There were problems from an industrial perspective.
（４１題を解決するための手段〕
本発明者らは、アミノ酸を鉱酸の存在下メタノールと反
応させエステル化した後、濃縮によりメタノールを一部
除き、水と共沸し得る有機溶媒を加えて共沸脱水すれば
、アミノ酸メチルエステルの鉱酸塩を高収率で単離でき
ることを見いだし２、本発明を完成した。(Means for Solving Problem 41) The present inventors esterified an amino acid by reacting it with methanol in the presence of a mineral acid, removed part of the methanol by concentration, and added an organic solvent that can be azeotropic with water. They discovered that mineral acid salts of amino acid methyl esters can be isolated in high yield by azeotropic dehydration,2 and the present invention was completed.
本発明の原料であるアミノ酸は、天然物、非天然物を問
わず、また、ラセミ体、光学活性体のいずれであっても
よい。例えば、グリシン、アラニン、バリン、ロイシン
、イソロイシン、フェニルアデニン、セリン、スレオニ
ン等の中性アミノ酸、リジン、アルギニン等の塩基性ア
ミノ酸、アスパラギン酸、グルタミン酸等の酸性アミノ
酸およびそれらの官能基が保護された誘導体等である。The amino acids that are the raw materials of the present invention may be natural or non-natural, and may be racemic or optically active. For example, neutral amino acids such as glycine, alanine, valine, leucine, isoleucine, phenyladenine, serine, and threonine, basic amino acids such as lysine and arginine, acidic amino acids such as aspartic acid and glutamic acid, and their functional groups are protected. derivatives, etc.
本発明で用い得る鉱酸は、アミノ酸のアミノ基と塩を形
成するとともに、エステル化の触媒となるものであるが
、−船釣には塩酸、硫酸、硝酸、リン酸等の鉱酸が用い
られる。好ましくは、エステル化反応後、過剰に用いた
鉱酸を容易に除き得る塩酸が適当である。The mineral acids that can be used in the present invention form salts with the amino groups of amino acids and serve as catalysts for esterification. It will be done. Hydrochloric acid is preferably used from which excess mineral acid can be easily removed after the esterification reaction.
本発明におけるエステル化の条件は特に限定されるもの
ではなく、用いるアミノ酸のエステル化の難易度を考慮
し温度、時間、原料のモル比等の条件は適宜選択しうる
０通常、室温で数日放置するか、または、メタノールの
還流温度近くまで加温して数時間反応させる方法がとら
れる。The conditions for esterification in the present invention are not particularly limited, and conditions such as temperature, time, and molar ratio of raw materials can be selected as appropriate in consideration of the difficulty of esterification of the amino acid used. Usually, at room temperature for several days. Either the mixture is left to stand, or the mixture is heated to near the reflux temperature of methanol and allowed to react for several hours.
反応後、減圧下または常圧下メタノールな留去して、奮
発残分全量に対して５〜２０％のメタノールが残る程度
まで濃縮するのが好ましい、これ以上メタノールを除く
ためには、高減圧度下においても高温長時間の操作が必
要であり、エステルの加水分解が進んで収率低下をきた
す、また、メタノールの残存量がこれより多いと、次の
操作で有機溶媒を加え、水を共沸で除く際に、主にメタ
ノールと有機溶媒が先に共沸で留出するために、効率よ
く共沸脱水することができない。After the reaction, it is preferable to distill off the methanol under reduced pressure or normal pressure and concentrate to the extent that 5 to 20% methanol remains based on the total amount of the ejected residue.To remove more methanol, use a high vacuum degree. Even at low temperatures, long-term operations at high temperatures are required, and the hydrolysis of the ester progresses, resulting in a decrease in yield.Also, if the amount of methanol remaining is greater than this, an organic solvent must be added in the next operation to co-mix water. When removing by boiling, the methanol and organic solvent are first distilled off azeotropically, making it impossible to efficiently perform azeotropic dehydration.
本発明の方法に用いる有機溶媒は、水と共沸混合物をつ
くるもので、反応混合物の構成成分に対して不活性なも
のであればなんでもよい０例えば、ベンゼン、トルエン
、ｎ−ヘキサン、シクロヘキサン等の炭化水素類、クロ
ロホルム、ジクロルエタン、四塩化炭素、１，２−ジク
ロルエタン、１゜１．２− トリクロルエタン、クロル
ベンゼン等のハロゲン化炭化水素、エチルエーテル、ブ
チルエーテル、テトラヒドロフラン、ジオキサン等のエ
ーテル類、酢酸メチル、プロピオン酸メチル等の工′ス
テル類が挙げられる。The organic solvent used in the method of the present invention may be any organic solvent as long as it forms an azeotrope with water and is inert to the constituent components of the reaction mixture.For example, benzene, toluene, n-hexane, cyclohexane, etc. hydrocarbons, chloroform, dichloroethane, carbon tetrachloride, 1,2-dichloroethane, 1゜1.2-trichloroethane, halogenated hydrocarbons such as chlorobenzene, ethers such as ethyl ether, butyl ether, tetrahydrofuran, dioxane, Examples include esters such as methyl acetate and methyl propionate.
共沸操作は、常圧下または減圧下で行うことができるが
、高温ではアミノ酸のラセミ化やエステルの加水分解が
起こるため、８０℃以下で行うことが好ましい。The azeotropic operation can be carried out under normal pressure or reduced pressure, but is preferably carried out at 80° C. or lower, since racemization of amino acids and hydrolysis of esters occur at high temperatures.
共沸脱水後は、そのまま乾燥して結晶あるいはオイル状
の目的物を得ることができる。また、結晶が析出してい
る場合は、濾過、乾燥、により目的物を得ることができ
る。さらに、次の工程で用いられる溶媒を加え、そのま
ま、あるいは残存溶媒を留出させて除くことにより、次
の工程に用いることもできる。After azeotropic dehydration, the desired product can be obtained in the form of crystals or oil by drying as it is. In addition, if crystals are precipitated, the desired product can be obtained by filtration and drying. Furthermore, it can be used in the next step by adding the solvent to be used in the next step and removing it as is or by distilling off the remaining solvent.
（作用および効果〕
本発明の方法によれば、メタノール中生成したアミノ酸
のメチルエステルを、単離工程における加水分解反応を
伴うことなく高収率で、かつ効率よく製造することがで
きる。(Functions and Effects) According to the method of the present invention, the methyl ester of an amino acid produced in methanol can be efficiently produced in high yield without involving a hydrolysis reaction in the isolation step.
（実施例〕 以下、実施例によって本発明の方法を詳しく説明する。(Example〕 Hereinafter, the method of the present invention will be explained in detail with reference to Examples.
実施例！
Ｌ−アラニン１０．ｈを、塩化水素１２ｇを含むメタノ
ール３８ｇに加え、２０°Ｃで撹拌下放置する０反応液
の高速液体クロマトグラフィーによる分析の結果、２４
時間後のし一アラニンメチルエステルへの転化率は９９
％以上に達した。Example! L-alanine 10. As a result of high performance liquid chromatography analysis of the reaction solution, which was added to 38 g of methanol containing 12 g of hydrogen chloride and left under stirring at 20°C, 24
The conversion rate to mono-alanine methyl ester after hours was 99
reached more than %.
反応後、留出残分の重量が１８．４ｇになるまで、減圧
下５０℃以下でメタノールを留去する３次に、トルエン
５０ｇを加え同じく減圧下トルエンと水を留出させると
全体が結晶化する。トルエンの留出がほとんどなくなっ
た所で、トルエン５０ｇを加えてスラリー化し、濾過、
乾燥することにより１５．８ｇの結晶を得た。After the reaction, methanol is distilled off under reduced pressure at 50°C or less until the weight of the distillate residue becomes 18.4 g. 3. Next, 50 g of toluene is added and toluene and water are distilled out under reduced pressure, and the whole becomes crystallized. become When almost no toluene was distilled out, 50 g of toluene was added to form a slurry, filtered,
By drying, 15.8 g of crystals were obtained.
この結晶の融点は１１０″Ｃであり、元素分析の結果は
Ｌ−アラニンメチルエステル塩酸塩に一致した。The melting point of this crystal was 110''C, and the results of elemental analysis were consistent with L-alanine methyl ester hydrochloride.
元素分析（ｉ１！（％） Ｃ４ＨＩＩＣＩ ＮｏｔＣ
ＨＮ Ｃ１
実測（ｉ ３４．３５ ７．３５ １０゜００ ２４
．８計算値 ３４．４２ ７．２２ １０．０３ ２５
．４この結晶を、高速液体クロマトグラフィーで分析し
た結果、純度９７．５％であり、未反応の■２−アラニ
ンは１．２％であった。収率９８．１％。Elemental analysis (i1! (%) C4HIICI NotC
HN C1 Actual measurement (i 34.35 7.35 10°00 24
．． 8 Calculated value 34.42 7.22 10.03 25
．． 4 This crystal was analyzed by high performance liquid chromatography, and the purity was 97.5%, and unreacted 2-alanine was 1.2%. Yield 98.1%.
比較例１
実施例１と同様の反応を行った後、メタノールを減圧下
′ａ縮して、さらにメタノール５０ｇを加え濃縮する操
作を２回繰り返す、得られたオイル状残渣にエチルエー
テルを加えて結晶化し、濾過、乾燥することによりＬｌ
、Ｏｇの結晶を得た。高速液体クロマトグラフィーによ
る分析の結果、純度９３．６％であり、未反応のＩ４−
アラニンを３．４％含んでいた。収率６５．８％。Comparative Example 1 After carrying out the same reaction as in Example 1, methanol was condensed under reduced pressure, 50 g of methanol was further added, and the operation of concentrating was repeated twice. Ethyl ether was added to the obtained oily residue. By crystallizing, filtering and drying Ll
, Og crystals were obtained. As a result of high performance liquid chromatography analysis, the purity was 93.6%, indicating that unreacted I4-
It contained 3.4% alanine. Yield 65.8%.
実施例２
Ｌ−アラニンのかわりにＬ−フェニルアラニン１０．０
ｇを用いた以外は、実施例１と同様にしてエステル化を
行なった。メタノールを濃縮する過程で結晶が析出した
が、そのままトルエン５０ｇを加えて共沸脱水を行い、
さらにトルエン５０ｇを加えて濾過、乾燥することによ
り結晶１３．１ｇを得た。Example 2 L-phenylalanine 10.0 instead of L-alanine
Esterification was carried out in the same manner as in Example 1 except that g was used. Crystals precipitated during the process of concentrating methanol, but 50 g of toluene was added as it was to perform azeotropic dehydration.
Further, 50 g of toluene was added, filtered, and dried to obtain 13.1 g of crystals.
この結晶の融点は１１６’Ｃであり、元素分析の結果は
Ｌ−フェニルアラニンメチルエステル塩酸塩に一致した
。The melting point of this crystal was 116'C, and the results of elemental analysis were consistent with L-phenylalanine methyl ester hydrochloride.
元素分析＋１ （％） Ｃ，ｏＨ＋、Ｃ＋ ＮｏＩＣ
ＨＮ Ｃ１
実測（直 ５５．２２ ７．０１ ６．２１
１５．８計算値 ５５．６８ ６．５４ ６．４９ １
６．４この結晶を、高速液体クロマトグラフィーで分析
した結果、純度９６．７％であり、未反応のし一アラニ
ンは２．１％であった。収率９７．０％。Elemental analysis +1 (%) C, oH+, C+ NoIC
HN C1 Actual measurement (direct 55.22 7.01 6.21
15.8 Calculated value 55.68 6.54 6.49 1
6.4 Analysis of this crystal by high performance liquid chromatography revealed that the purity was 96.7%, and unreacted mono-alanine was 2.1%. Yield 97.0%.
比較例２
実施例２と同様の反応を行った後、メタノールを減圧下
濃縮して、さらにメタノール５０ｇを加え濃縮する操作
を２回繰り返す、得られた結晶化した残渣にエチルエー
テルを加えてスラリー化し、濾過、乾燥することにより
１２．８ ｇの結晶を得た。Comparative Example 2 After carrying out the same reaction as in Example 2, methanol was concentrated under reduced pressure, and the operation of adding 50 g of methanol and concentrating was repeated twice. Ethyl ether was added to the obtained crystallized residue to form a slurry. 12.8 g of crystals were obtained by drying, filtering, and drying.
高速液体クロマトグラフィーによる分析の結果、純度９
３．３％であり、未反応のし一フェニルアラニンを５．
１％含んでいた。収率９１．３％。As a result of analysis by high performance liquid chromatography, purity is 9.
3.3%, and unreacted phenylalanine was added to 5.3%.
It contained 1%. Yield 91.3%.
実施例３
■、−アスパラギン酸１０．０ ｇを、塩化水素１２ｇ
を含むメタノール３８ｇに加え、４０°Ｃで撹拌上反応
する０反応液の高速液体クロマトグラフィーによる分析
の結果、４時間後のし一アスパラギン酸ジメチルエステ
ルへの転化率は９９％以上に達した。Example 3 ■, -10.0 g of aspartic acid and 12 g of hydrogen chloride
As a result of analysis by high performance liquid chromatography of the reaction solution, which was added to 38 g of methanol containing 38 g of methanol and reacted at 40° C. with stirring, the conversion rate to dimethyl aspartate reached 99% or more after 4 hours.
反応後、留出残分の重量が１７．５ ｇになるまで、減
圧下５０℃以下でメタノールを留去させる。次に、トル
エン５０ｇを加え同じく減圧下トルエンと水を留出させ
る。トルエンの留出がほとんどなくなった所で、しばら
く放置すると結晶化するので、トルエン５０ｇを加えて
スラリー化し、濾過、乾燥することにより１４．９ｇの
結晶を得た。After the reaction, methanol is distilled off under reduced pressure at 50° C. or lower until the weight of the distillate residue is 17.5 g. Next, 50 g of toluene is added and toluene and water are distilled out under reduced pressure. When almost no toluene was distilled out, crystallization would occur if left for a while, so 50 g of toluene was added to form a slurry, filtered, and dried to obtain 14.9 g of crystals.
この結晶の融点は１１６℃であり、元素分析の結果はＩ
、−アスパラギン酸ジメチルエステル塩酸塩に一致した
。The melting point of this crystal is 116°C, and the results of elemental analysis are I
,-aspartic acid dimethyl ester hydrochloride.
元素分析値（％） Ｃ，Ｈ，、ＣＩ Ｎｏ。Elemental analysis value (%) C, H, CI No.
ＣＨＮ Ｃ１
実測債 ３５．９１ ６．８８ ６．７５ １６．６計
算値 ３６．４７ ６゜１２ ７．０９ １７．９この
結晶を、高速液体クロマトグラフィーで分析した結果、
純度９６．２％であり、未反応のし一アスパラギン酸と
Ｌ−アスパラギン酸のα及びβ−モノメチルエステルの
合計は２．８％であった。収率９６．６％。CHN C1 Measured bond 35.91 6.88 6.75 16.6 Calculated value 36.47 6°12 7.09 17.9 As a result of analyzing this crystal by high performance liquid chromatography,
The purity was 96.2%, and the total amount of unreacted monoaspartic acid and α- and β-monomethyl esters of L-aspartic acid was 2.8%. Yield 96.6%.
比較例３
実施例３と同様の反応を行った後、メタノールを減圧上
濃縮して、さらにメタノール５０ｇを加え濃縮する操作
を２回繰り返す、得られたオイル状残渣にエチルエーテ
ルを加えて結晶化し、濾過、乾燥することにより１３．
８ｇの結晶を得た。高速液体クロマトグラフィーによる
分析の結果、純度８１．９％であり、未反応のし一アス
パラギン酸とＬ−アスパラギン酸のα及びβ−モノメチ
ルエステルの合計は１４．１％であった。収率７６．１
％。Comparative Example 3 After carrying out the same reaction as in Example 3, methanol was concentrated under reduced pressure, and the operation of adding 50 g of methanol and concentrating was repeated twice. Ethyl ether was added to the obtained oily residue to crystallize it. 13. by filtration and drying.
8 g of crystals were obtained. As a result of analysis by high performance liquid chromatography, the purity was 81.9%, and the total amount of unreacted mono-aspartic acid and α- and β-monomethyl esters of L-aspartic acid was 14.1%. Yield 76.1
%.
実施例４
Ｌ−セリン１０．０ ｇを、塩化水素１２ｇを含むメタ
ノール３８ｇに加え、４０℃で撹拌上反応する０反応液
の高速液体クロマトグラフィーによる分析の結果、４時
間後のし一セリンメチルエステルへの転化率は９９％以
上に達した。Example 4 10.0 g of L-serine was added to 38 g of methanol containing 12 g of hydrogen chloride, and the reaction mixture was stirred and reacted at 40° C. Analysis of the reaction solution by high performance liquid chromatography revealed that methyl serine was present after 4 hours. The conversion rate to ester reached over 99%.
反応後、留出残分の重量が１８．２ｇになるまで、減圧
下５０℃以下でメタノールを留去させる。メタノールを
濃縮する過程で結晶が析出したが、そのままトルエン５
０ｇを加え、同じく減圧下トルエンと水を留出させる。After the reaction, methanol is distilled off under reduced pressure at 50° C. or lower until the weight of the distillate residue becomes 18.2 g. Crystals precipitated during the process of concentrating methanol, but they were added to toluene as they were.
0 g was added, and toluene and water were similarly distilled off under reduced pressure.
トルエンの留出がほとんどなくなった所で、トルエン５
０ｇを加えてスラリー化し、濾過、乾燥することにより
１５．１ ｇの結晶を得た。At the point where toluene distillation is almost gone, toluene 5
0 g was added to form a slurry, filtered and dried to obtain 15.1 g of crystals.
この結晶の融点は１６６°Ｃであり、元素分析の結果は
Ｌ−セリンメチルエステル塩酸塩に一致した元素分析値
（％） Ｃ，Ｈ，、ＣＩ ＮｏＩＣＨＮ Ｃ１
実測値 ２９．９５ ７．５４ ８．４３ ２２．３計
算（直 ３０．６８ ７．０８ ８．９４ ２２
．にの結晶を、高速液体クロマトグラフィーで分析した
結果、純［９６，７％であり、未反応のし一セリンは２
．３％であった。収率９８．４％。The melting point of this crystal is 166°C, and the elemental analysis results are consistent with L-serine methyl ester hydrochloride.Elemental analysis value (%) C, H,, CI NoICHN C1 Actual value 29.95 7.54 8. 43 22.3 calculation (direct 30.68 7.08 8.94 22
．． Analysis of the crystals by high performance liquid chromatography revealed that the crystals were pure [96.7%], and the unreacted serine was 2.
．． It was 3%. Yield 98.4%.
比較例４
実施例４と同様の反応を行った後、メタノールを減圧下
′ａ！１１して、さらにメタノール５０ｇを加え濃縮す
る操作を２回繰り返す。得られた結晶化した残渣にエチ
ルエーテルを加えてスラリー化し、濾過、乾燥すること
により１４．４ｇの結晶を得た。Comparative Example 4 After carrying out the same reaction as in Example 4, methanol was added under reduced pressure'a! Step 11, add 50 g of methanol, and repeat the operation of concentrating twice. Ethyl ether was added to the obtained crystallized residue to form a slurry, which was then filtered and dried to obtain 14.4 g of crystals.
高速液体クロマトグラフィーによる分析の結果、純度９
４．０％であり、未反応のし一セリンを３．２％含んで
いた。収率９１．０％。As a result of analysis by high performance liquid chromatography, purity is 9.
4.0%, and contained 3.2% of unreacted serine. Yield 91.0%.
実施例５
Ｌ−アスパラギン酸のかわりにＬ−リジン塩酸塩１０．
０ ｇを用いた以外は、実施例３と同様にしてエステル
化を行なった０反応中に結晶が析出し、反応液の高速液
体クロマトグラフィーによる分析の結果、４時間後のＬ
−リジンメチルエステルへの転化率は９９％以上に達し
た。Example 5 L-lysine hydrochloride instead of L-aspartic acid 10.
Crystals were precipitated during the esterification reaction in which esterification was carried out in the same manner as in Example 3, except that 0 g was used, and as a result of analysis of the reaction solution by high performance liquid chromatography, L after 4 hours was
-The conversion rate to lysine methyl ester reached 99% or more.
反応後、留出残分の重量が１９．９ ｇになるまで、減
圧下５０℃以下でメタノールを留去させる０次に、トル
エン５０ｇを加え、同じく減圧下トルエンと水を留出さ
せる。トルエンの留出がほとんどなくなった所で、トル
エン５０ｇを加えてスラリー化し、濾過、乾燥すること
により１６．０ ｇの結晶を得たこの結晶の融点は２１
０”Ｃであり、元素分析の結果は■、−リジンメチルエ
ステルニ塩酸塩に一致した。After the reaction, methanol is distilled off under reduced pressure at 50° C. or below until the weight of the distilled residue becomes 19.9 g. Next, 50 g of toluene is added, and toluene and water are distilled off under reduced pressure as well. When almost no toluene was distilled out, 50 g of toluene was added to form a slurry, filtered, and dried to obtain 16.0 g of crystals. The melting point of these crystals was 21.
0''C, and the results of elemental analysis were consistent with ■,-lysine methyl ester dihydrochloride.
元素分析値（％） Ｃｔ Ｈ＋ ＊ ＣＩ ｘ Ｎ
ｘ ＯｘＣＨＮ Ｃ１
実測値 ３６．０２ ８．０３１１．９７ ２９．７計
夏値 ３６．０６ ７．７８１２．０２ ３０．４この
結晶を、高速液体クロマトグラフィーで分析した結果、
純度９５．８％であり、未反応のｌ、 ＩＪジンは３
．１％であった。収率９６．１％。Elemental analysis value (%) Ct H+ * CI x N
x OxCHN C1 Actual value 36.02 8.0311.97 29.7 Total summer value 36.06 7.7812.02 30.4 As a result of analyzing this crystal by high performance liquid chromatography,
The purity is 95.8%, and the unreacted l, IJ gin is 3
．． It was 1%. Yield 96.1%.
比較例５
実施例５と同様の反応を行った後、メタノールを減圧下
ｉ４縮して、さらにメタノール５０ｇを加え濃縮する操
作を２回繰り返す。得られた結晶化した残渣にエチルエ
ーテルを加えてスラリー化し、濾過、乾燥することによ
り１２．３ｇの結晶を得た。Comparative Example 5 After carrying out the same reaction as in Example 5, methanol was condensed under reduced pressure, and the operation of adding 50 g of methanol and concentrating was repeated twice. Ethyl ether was added to the obtained crystallized residue to form a slurry, which was then filtered and dried to obtain 12.3 g of crystals.
高速液体クロマトグラフィーによる分析の結果、純度９
２．３％であり、未反応のし一リジンを５．６％含んで
いた。収率７６．９％。As a result of analysis by high performance liquid chromatography, purity is 9.
It contained 5.6% of unreacted lysine. Yield 76.9%.
実施例６〜８
トルエンのかわりに、表１に示した有機溶媒を用いて、
共沸脱水を行った以外は実施例３と同様の反応と後処理
を行い、それぞれ表１に示した結果を得た。Examples 6 to 8 Using the organic solvents shown in Table 1 instead of toluene,
The reaction and post-treatment were carried out in the same manner as in Example 3, except that azeotropic dehydration was carried out, and the results shown in Table 1 were obtained.
Claims (1)
のメチルエステルの鉱酸塩を製造する方法において、エ
ステル化反応終了後、過剰のメタノールを除き、続いて
水と共沸しうる有機溶媒を加え、共沸脱水することを特
徴とするアミノ酸メチルエステル鉱酸塩の製造法。1) In the method of producing a mineral acid salt of a methyl ester of an amino acid from an amino acid and methanol in the presence of a mineral acid, after the esterification reaction is completed, excess methanol is removed, and then an organic solvent that can be azeotroped with water is added. , a method for producing an amino acid methyl ester mineral salt, the method comprising azeotropic dehydration.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63119374A JP2728883B2 (en) | 1988-05-18 | 1988-05-18 | Method for producing amino acid methylsulfate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63119374A JP2728883B2 (en) | 1988-05-18 | 1988-05-18 | Method for producing amino acid methylsulfate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH01290655A true JPH01290655A (en) | 1989-11-22 |
| JP2728883B2 JP2728883B2 (en) | 1998-03-18 |
Family
ID=14759929
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP63119374A Expired - Lifetime JP2728883B2 (en) | 1988-05-18 | 1988-05-18 | Method for producing amino acid methylsulfate |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2728883B2 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5113009A (en) * | 1988-12-27 | 1992-05-12 | Mitsui Toatsu Chemicals, Incorporated | Preparation and isolation of mineral acid salt of an amino acid methyl ester |
| JP2002255876A (en) * | 2001-02-23 | 2002-09-11 | Showa Denko Kk | Method for purifying and producing propargyl alcohol |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5740456A (en) * | 1980-08-26 | 1982-03-06 | Mitsui Toatsu Chem Inc | Separation of aminoalkanol sulfuric acid ester |
| JPS6174588A (en) * | 1984-09-12 | 1986-04-16 | バスフ アクチェン ゲゼルシャフト | Production of lactic ester |
-
1988
- 1988-05-18 JP JP63119374A patent/JP2728883B2/en not_active Expired - Lifetime
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5740456A (en) * | 1980-08-26 | 1982-03-06 | Mitsui Toatsu Chem Inc | Separation of aminoalkanol sulfuric acid ester |
| JPS6174588A (en) * | 1984-09-12 | 1986-04-16 | バスフ アクチェン ゲゼルシャフト | Production of lactic ester |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5113009A (en) * | 1988-12-27 | 1992-05-12 | Mitsui Toatsu Chemicals, Incorporated | Preparation and isolation of mineral acid salt of an amino acid methyl ester |
| JP2002255876A (en) * | 2001-02-23 | 2002-09-11 | Showa Denko Kk | Method for purifying and producing propargyl alcohol |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2728883B2 (en) | 1998-03-18 |
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