FR2551060A1 - Procede de preparation de gros cristaux d'acide n-benzyloxycarbonyl-l-aspartique et gros cristaux de n-benzyloxycarbonyl-l-aspartique obtenus - Google Patents
Procede de preparation de gros cristaux d'acide n-benzyloxycarbonyl-l-aspartique et gros cristaux de n-benzyloxycarbonyl-l-aspartique obtenus Download PDFInfo
- Publication number
- FR2551060A1 FR2551060A1 FR8413226A FR8413226A FR2551060A1 FR 2551060 A1 FR2551060 A1 FR 2551060A1 FR 8413226 A FR8413226 A FR 8413226A FR 8413226 A FR8413226 A FR 8413226A FR 2551060 A1 FR2551060 A1 FR 2551060A1
- Authority
- FR
- France
- Prior art keywords
- acid
- asp
- crystals
- benzyloxycarbonyl
- temperature
- 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.)
- Withdrawn
Links
- 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 title claims abstract description 103
- 239000013078 crystal Substances 0.000 title claims abstract description 85
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 8
- 238000000034 method Methods 0.000 claims abstract description 52
- 239000002253 acid Substances 0.000 claims abstract description 31
- 229910052751 metal Inorganic materials 0.000 claims abstract description 16
- 239000002184 metal Substances 0.000 claims abstract description 16
- 150000003839 salts Chemical class 0.000 claims abstract description 16
- 239000007864 aqueous solution Substances 0.000 claims abstract description 10
- 239000012670 alkaline solution Substances 0.000 claims abstract description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 28
- 239000000243 solution Substances 0.000 claims description 23
- 229960005261 aspartic acid Drugs 0.000 claims description 13
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 10
- 239000011707 mineral Substances 0.000 claims description 10
- 230000020477 pH reduction Effects 0.000 claims description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 8
- 238000001816 cooling Methods 0.000 claims description 5
- 239000002002 slurry Substances 0.000 claims description 5
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 claims description 4
- 238000010899 nucleation Methods 0.000 claims description 2
- GSYSFVSGPABNNL-UHFFFAOYSA-N methyl 2-dimethoxyphosphoryl-2-(phenylmethoxycarbonylamino)acetate Chemical group COC(=O)C(P(=O)(OC)OC)NC(=O)OCC1=CC=CC=C1 GSYSFVSGPABNNL-UHFFFAOYSA-N 0.000 claims 1
- 238000010792 warming Methods 0.000 claims 1
- 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 10
- 108010011485 Aspartame Proteins 0.000 abstract description 9
- 235000010357 aspartame Nutrition 0.000 abstract description 9
- 239000000605 aspartame Substances 0.000 abstract description 9
- 229960003438 aspartame Drugs 0.000 abstract description 9
- 238000002360 preparation method Methods 0.000 abstract description 6
- 230000015572 biosynthetic process Effects 0.000 abstract description 5
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 230000002349 favourable effect Effects 0.000 abstract 1
- 239000000047 product Substances 0.000 description 46
- 239000011541 reaction mixture Substances 0.000 description 36
- 238000002425 crystallisation Methods 0.000 description 26
- 230000008025 crystallization Effects 0.000 description 25
- 239000012535 impurity Substances 0.000 description 24
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 17
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 11
- CKLJMWTZIZZHCS-UWTATZPHSA-N L-Aspartic acid Natural products OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 description 11
- 239000000523 sample Substances 0.000 description 10
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 9
- 108010016626 Dipeptides Proteins 0.000 description 9
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 239000011780 sodium chloride Substances 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 8
- 239000005457 ice water Substances 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 239000012736 aqueous medium Substances 0.000 description 5
- 238000005119 centrifugation Methods 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 5
- PIZLBWGMERQCOC-UHFFFAOYSA-N dibenzyl carbonate Chemical compound C=1C=CC=CC=1COC(=O)OCC1=CC=CC=C1 PIZLBWGMERQCOC-UHFFFAOYSA-N 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 4
- 235000019445 benzyl alcohol Nutrition 0.000 description 3
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 3
- 229940073608 benzyl chloride Drugs 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 238000009833 condensation Methods 0.000 description 3
- 230000005494 condensation Effects 0.000 description 3
- -1 disodium salt Chemical class 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000012467 final product Substances 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 101100107064 Drosophila melanogaster Zasp52 gene Proteins 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 238000010924 continuous production Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 238000000638 solvent extraction Methods 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- YIELQSHMEZQETN-QWRGUYRKSA-N (2s)-2-[[(2s)-3-carboxy-2-(phenylmethoxycarbonylamino)propanoyl]amino]butanedioic acid Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)OCC1=CC=CC=C1 YIELQSHMEZQETN-QWRGUYRKSA-N 0.000 description 1
- QNRATNLHPGXHMA-XZHTYLCXSA-N (r)-(6-ethoxyquinolin-4-yl)-[(2s,4s,5r)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl]methanol;hydrochloride Chemical compound Cl.C([C@H]([C@H](C1)CC)C2)CN1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OCC)C=C21 QNRATNLHPGXHMA-XZHTYLCXSA-N 0.000 description 1
- UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 238000010420 art technique Methods 0.000 description 1
- 238000010923 batch production Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000000295 fuel oil Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 235000013615 non-nutritive sweetener Nutrition 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000021092 sugar substitutes Nutrition 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C269/08—Separation; Purification; Stabilisation; Use of additives
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Peptides Or Proteins (AREA)
- Seasonings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/526,580 US4570015A (en) | 1983-08-26 | 1983-08-26 | Preparation of large crystals of N-benzyloxycarbonyl-L-aspartic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| FR2551060A1 true FR2551060A1 (fr) | 1985-03-01 |
Family
ID=24097911
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FR8413226A Withdrawn FR2551060A1 (fr) | 1983-08-26 | 1984-08-24 | Procede de preparation de gros cristaux d'acide n-benzyloxycarbonyl-l-aspartique et gros cristaux de n-benzyloxycarbonyl-l-aspartique obtenus |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US4570015A (enExample) |
| JP (1) | JPS60185755A (enExample) |
| KR (1) | KR850001770A (enExample) |
| DE (1) | DE3431246A1 (enExample) |
| ES (1) | ES535388A0 (enExample) |
| FR (1) | FR2551060A1 (enExample) |
| GB (1) | GB2149397A (enExample) |
| IT (1) | IT1177976B (enExample) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR112021008112A2 (pt) * | 2018-11-05 | 2021-08-03 | Xianfeng Peng | uso de derivativo de ácido espártico na preparação de aditivo para alimentação animal. |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3957864A (en) * | 1975-03-31 | 1976-05-18 | Commercial Solvents Corporation | Process for recovery of 1-glutamic acid |
| GB2069484A (en) * | 1980-02-04 | 1981-08-26 | Ajinomoto Kk | Method of producing n-benzyloxycarbonyl-l-aspartic acid |
| US4293706A (en) * | 1980-06-19 | 1981-10-06 | Ppg Industries, Inc. | Preparation of N-benzyloxycarbonyl aspartic acid |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH553751A (de) * | 1970-05-19 | 1974-09-13 | Stamicarbon | Verfahren zur herstellung von aspartylaminosaeure-estern. |
| US4450284A (en) * | 1981-08-10 | 1984-05-22 | Ppg Industries, Inc. | Method for purifying N-benzyloxycarbonyl aspartic acid |
-
1983
- 1983-08-26 US US06/526,580 patent/US4570015A/en not_active Expired - Lifetime
-
1984
- 1984-08-21 GB GB08421156A patent/GB2149397A/en not_active Withdrawn
- 1984-08-24 FR FR8413226A patent/FR2551060A1/fr not_active Withdrawn
- 1984-08-24 DE DE19843431246 patent/DE3431246A1/de not_active Withdrawn
- 1984-08-24 ES ES535388A patent/ES535388A0/es active Granted
- 1984-08-25 KR KR1019840005196A patent/KR850001770A/ko not_active Withdrawn
- 1984-08-27 IT IT48762/84A patent/IT1177976B/it active
- 1984-08-27 JP JP59176885A patent/JPS60185755A/ja active Granted
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3957864A (en) * | 1975-03-31 | 1976-05-18 | Commercial Solvents Corporation | Process for recovery of 1-glutamic acid |
| GB2069484A (en) * | 1980-02-04 | 1981-08-26 | Ajinomoto Kk | Method of producing n-benzyloxycarbonyl-l-aspartic acid |
| US4293706A (en) * | 1980-06-19 | 1981-10-06 | Ppg Industries, Inc. | Preparation of N-benzyloxycarbonyl aspartic acid |
Also Published As
| Publication number | Publication date |
|---|---|
| US4570015A (en) | 1986-02-11 |
| GB2149397A (en) | 1985-06-12 |
| IT1177976B (it) | 1987-09-03 |
| ES8600209A1 (es) | 1985-10-01 |
| JPS60185755A (ja) | 1985-09-21 |
| IT8448762A1 (it) | 1986-02-27 |
| JPH0587501B2 (enExample) | 1993-12-16 |
| ES535388A0 (es) | 1985-10-01 |
| GB8421156D0 (en) | 1984-09-26 |
| IT8448762A0 (it) | 1984-08-27 |
| DE3431246A1 (de) | 1985-03-21 |
| KR850001770A (ko) | 1985-04-01 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| ST | Notification of lapse |