CA1258749A - METHOD OF PREPARING .alpha.-L-ASPARTYL-L-PHENYLALANINE METHYL ESTER AND ITS HYDROCHLORIDE - Google Patents
METHOD OF PREPARING .alpha.-L-ASPARTYL-L-PHENYLALANINE METHYL ESTER AND ITS HYDROCHLORIDEInfo
- Publication number
- CA1258749A CA1258749A CA000455146A CA455146A CA1258749A CA 1258749 A CA1258749 A CA 1258749A CA 000455146 A CA000455146 A CA 000455146A CA 455146 A CA455146 A CA 455146A CA 1258749 A CA1258749 A CA 1258749A
- Authority
- CA
- Canada
- Prior art keywords
- hydrochloride
- hydrochloric acid
- aspartyl
- ester
- volume
- 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.)
- Expired
Links
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 title claims abstract description 78
- 238000000034 method Methods 0.000 title claims description 21
- YZQCXOFQZKCETR-UHFFFAOYSA-N aspartyl-phenylalanine Chemical compound OC(=O)CC(N)C(=O)NC(C(O)=O)CC1=CC=CC=C1 YZQCXOFQZKCETR-UHFFFAOYSA-N 0.000 title 1
- 239000012046 mixed solvent Substances 0.000 claims abstract description 8
- OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 claims abstract description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 60
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 15
- 125000005907 alkyl ester group Chemical group 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 7
- 150000002148 esters Chemical class 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 230000003472 neutralizing effect Effects 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 229960000443 hydrochloric acid Drugs 0.000 claims 11
- 235000011167 hydrochloric acid Nutrition 0.000 claims 11
- 239000003513 alkali Substances 0.000 claims 2
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 claims 1
- 230000007062 hydrolysis Effects 0.000 abstract description 8
- 238000006460 hydrolysis reaction Methods 0.000 abstract description 8
- 235000003599 food sweetener Nutrition 0.000 abstract description 3
- 108090000765 processed proteins & peptides Proteins 0.000 abstract description 3
- 239000003765 sweetening agent Substances 0.000 abstract description 3
- 150000004702 methyl esters Chemical class 0.000 abstract 2
- 239000000243 solution Substances 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 7
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 6
- 239000013078 crystal Substances 0.000 description 5
- 238000005886 esterification reaction Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 4
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 230000032050 esterification Effects 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000012452 mother liquor Substances 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- OSEHTEQTVJQGDE-RYUDHWBXSA-N (3s)-3-formamido-4-[[(2s)-1-methoxy-1-oxo-3-phenylpropan-2-yl]amino]-4-oxobutanoic acid Chemical compound OC(=O)C[C@H](NC=O)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 OSEHTEQTVJQGDE-RYUDHWBXSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- XYXYXSKSTZAEJW-VIFPVBQESA-N (2s)-2-(phenylmethoxycarbonylamino)butanedioic acid Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)OCC1=CC=CC=C1 XYXYXSKSTZAEJW-VIFPVBQESA-N 0.000 description 1
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 1
- CKLJMWTZIZZHCS-UWTATZPHSA-N L-Aspartic acid Natural products OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 229960005261 aspartic acid Drugs 0.000 description 1
- 108010069205 aspartyl-phenylalanine Proteins 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- XTEGARKTQYYJKE-UHFFFAOYSA-N chloric acid Chemical compound OCl(=O)=O XTEGARKTQYYJKE-UHFFFAOYSA-N 0.000 description 1
- 229940005991 chloric acid Drugs 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 238000010931 ester hydrolysis Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 230000004992 fission Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 125000001145 hydrido group Chemical group *[H] 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- VSDUZFOSJDMAFZ-VIFPVBQESA-N methyl L-phenylalaninate Chemical compound COC(=O)[C@@H](N)CC1=CC=CC=C1 VSDUZFOSJDMAFZ-VIFPVBQESA-N 0.000 description 1
- DFTMVZIUYVECNW-VKHMYHEASA-N n-[(3s)-2,5-dioxooxolan-3-yl]formamide Chemical compound O=CN[C@H]1CC(=O)OC1=O DFTMVZIUYVECNW-VKHMYHEASA-N 0.000 description 1
- 229960005190 phenylalanine Drugs 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06104—Dipeptides with the first amino acid being acidic
- C07K5/06113—Asp- or Asn-amino acid
- C07K5/06121—Asp- or Asn-amino acid the second amino acid being aromatic or cycloaliphatic
- C07K5/0613—Aspartame
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP58094477A JPS59219258A (ja) | 1983-05-28 | 1983-05-28 | α−Ｌ−アスパルチル−Ｌ−フエニルアラニンメチルエステル又はその塩酸塩の製法 |
| JP94477/1983 | 1983-05-28 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1258749A true CA1258749A (en) | 1989-08-22 |
Family
ID=14111354
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000455146A Expired CA1258749A (en) | 1983-05-28 | 1984-05-25 | METHOD OF PREPARING .alpha.-L-ASPARTYL-L-PHENYLALANINE METHYL ESTER AND ITS HYDROCHLORIDE |
Country Status (7)
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS59219258A (ja) * | 1983-05-28 | 1984-12-10 | Ajinomoto Co Inc | α−Ｌ−アスパルチル−Ｌ−フエニルアラニンメチルエステル又はその塩酸塩の製法 |
| US4618695A (en) * | 1983-06-02 | 1986-10-21 | Ajinomoto Co., Inc. | Method of preparing methyl ester and its hydrochloride |
| JPS60174799A (ja) * | 1984-02-21 | 1985-09-09 | Ajinomoto Co Inc | α−Ｌ−アスパルチル−Ｌ−フエニルアラニンメチルエステルの製造法 |
| JPH07636B2 (ja) * | 1984-12-17 | 1995-01-11 | 三井東圧化学株式会社 | Ｎ−ホルミル−α−アスパルチルフエニルアラニンの製造法 |
| CA1277098C (en) * | 1984-12-27 | 1990-11-27 | Mitsui Toatsu Chemicals, Inc. | Preparation process of -l-aspartyl-l-phenylalanine methyl ester |
| AU561384B2 (en) * | 1985-03-26 | 1987-05-07 | Mitsui Toatsu Chemicals Inc. | Preparation of -l-aspartyl-l-phenylalanine methyl ester or hydrochloride thereof |
| AU586669B2 (en) * | 1985-03-29 | 1989-07-20 | Mitsui Toatsu Chemicals Inc. | Preparation process of ```-L-aspartyl-L-phenylalanine methyl ester or hydrochloride thereof |
| US4677220A (en) * | 1985-10-31 | 1987-06-30 | Monsanto Company | Process for the preparation of α-L-aspartyl-L-phenylalanine methyl ester |
| JPS6383098A (ja) * | 1986-09-27 | 1988-04-13 | Ajinomoto Co Inc | α−Ｌ−アスパルチル−Ｌ−フエニルアラニン又はその誘導体の製造方法 |
| EP0270345B1 (en) * | 1986-12-05 | 1992-07-22 | MITSUI TOATSU CHEMICALS, Inc. | Preparation of alpha-l-aspartyl-l-phenyl-alanine methyl ester or hydrohalide thereof |
| JPH0832719B2 (ja) * | 1986-12-19 | 1996-03-29 | 三井東圧化学株式会社 | 吸湿性の小さいα−Ｌ−アスパルチル−Ｌ−フエニルアラニンメチルエステルの製造法 |
| JP2927070B2 (ja) * | 1991-05-23 | 1999-07-28 | 味の素株式会社 | α−Ｌ−アスパルチル−Ｌ−フェニルアラニンメチルエステルの製造方法 |
| US6657073B1 (en) | 1999-08-18 | 2003-12-02 | Daesang Corporation | Crystallization of α-L-aspartyl-L-phenylalanine methyl ester |
| EP3868472B1 (en) | 2015-06-19 | 2023-09-20 | Saudi Arabian Oil Company | Antifouling oligomerization catalyst systems |
| US11104621B2 (en) | 2016-01-07 | 2021-08-31 | Saudi Arabian Oil Company | Antifouling oligomerization catalyst systems |
| US10280125B2 (en) | 2016-12-07 | 2019-05-07 | Sumitomo Chemical Company, Limited | Process for selective ethylene oligomerization with antifouling components |
| WO2019060299A1 (en) | 2017-09-22 | 2019-03-28 | Saudi Arabian Oil Company | ONLINE PROCESS FOR MANUFACTURING CO-CATALYST OF ANTIFOULING AGENT FOR OLIGOMERIZING ETHYLENE |
| US11440980B2 (en) | 2020-07-22 | 2022-09-13 | Saudi Arabian Oil Company | Methods for forming ultra high molecular weight polyethylenes and methods for reducing contaminant content in such |
| WO2022115754A1 (en) | 2020-11-30 | 2022-06-02 | Saudi Arabian Oil Company | Catalyst systems |
| WO2022115748A1 (en) | 2020-11-30 | 2022-06-02 | Saudi Arabian Oil Company | Catalyst systems |
| US11458462B2 (en) | 2020-11-30 | 2022-10-04 | Saudi Arabian Oil Company | Catalyst systems |
| WO2022115750A1 (en) | 2020-11-30 | 2022-06-02 | Saudi Arabian Oil Company | Catalyst systems |
| WO2022115749A1 (en) | 2020-11-30 | 2022-06-02 | Saudi Arabian Oil Company | Catalyst systems |
| US11529622B2 (en) | 2021-03-12 | 2022-12-20 | Saudi Arabian Oil Company | Catalyst systems |
| WO2023027749A1 (en) | 2021-08-26 | 2023-03-02 | Saudi Arabian Oil Company | Catalyst systems |
| US11623901B1 (en) | 2022-08-31 | 2023-04-11 | Saudi Arabian Oil Company | Catalyst systems that include silyl ether moieties |
| US11639321B1 (en) | 2022-08-31 | 2023-05-02 | Saudi Arabian Oil Company | Catalyst systems that include meta-alkoxy substituted n-aryl bis-diphosphinoamine ligands |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS4941425B1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) * | 1970-10-26 | 1974-11-08 | ||
| US3933781A (en) * | 1973-11-05 | 1976-01-20 | Monsanto Company | Process for the preparation of α-L-aspartyl-L-phenylalanine alkyl esters |
| US4173562A (en) * | 1976-12-27 | 1979-11-06 | Monsanto Company | Process for the preparation of α-L-aspartyl-L-phenylalanine methyl ester |
| MX4704E (es) * | 1976-12-27 | 1982-08-04 | Monsanto Co | Procedimiento mejorado para la preparacion de ester metilico de alfa-l-aspartil-l-fenilalanina |
| US4111925A (en) * | 1977-10-14 | 1978-09-05 | Monsanto Company | Hydrolysis of esters of α-L-aspartyl-L-phenylalanine |
| JPS59219258A (ja) * | 1983-05-28 | 1984-12-10 | Ajinomoto Co Inc | α−Ｌ−アスパルチル−Ｌ−フエニルアラニンメチルエステル又はその塩酸塩の製法 |
-
1983
- 1983-05-28 JP JP58094477A patent/JPS59219258A/ja active Granted
-
1984
- 1984-05-17 US US06/611,531 patent/US4606854A/en not_active Expired - Lifetime
- 1984-05-21 EP EP84303419A patent/EP0127411B1/en not_active Expired
- 1984-05-21 DE DE8484303419T patent/DE3473266D1/de not_active Expired
- 1984-05-21 IE IE1257/84A patent/IE57517B1/en not_active IP Right Cessation
- 1984-05-25 CA CA000455146A patent/CA1258749A/en not_active Expired
- 1984-05-26 KR KR1019840002906A patent/KR900008012B1/ko not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| KR900008012B1 (ko) | 1990-10-29 |
| DE3473266D1 (en) | 1988-09-15 |
| EP0127411B1 (en) | 1988-08-10 |
| EP0127411A2 (en) | 1984-12-05 |
| EP0127411A3 (en) | 1985-09-18 |
| IE57517B1 (en) | 1992-10-07 |
| JPH0363556B2 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1991-10-01 |
| KR840009295A (ko) | 1984-12-26 |
| US4606854A (en) | 1986-08-19 |
| JPS59219258A (ja) | 1984-12-10 |
| IE841257L (en) | 1984-11-28 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |