CN104151171B - 一种拆分制备光学纯r-1-萘乙胺的方法 - Google Patents
一种拆分制备光学纯r-1-萘乙胺的方法 Download PDFInfo
- Publication number
- CN104151171B CN104151171B CN201410399401.9A CN201410399401A CN104151171B CN 104151171 B CN104151171 B CN 104151171B CN 201410399401 A CN201410399401 A CN 201410399401A CN 104151171 B CN104151171 B CN 104151171B
- Authority
- CN
- China
- Prior art keywords
- naphthylethylamine
- acetamide
- naphthalene ethylamine
- ethyl
- naphthyl
- 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.)
- Active
Links
- 230000003287 optical effect Effects 0.000 title claims description 5
- 238000005194 fractionation Methods 0.000 title claims 2
- 238000000034 method Methods 0.000 title abstract description 12
- RUJHATQMIMUYKD-UHFFFAOYSA-N 2-naphthalen-1-ylethanamine Chemical compound C1=CC=C2C(CCN)=CC=CC2=C1 RUJHATQMIMUYKD-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000003054 catalyst Substances 0.000 claims abstract description 9
- 238000002360 preparation method Methods 0.000 claims abstract description 8
- 239000002994 raw material Substances 0.000 claims abstract description 6
- 108010084311 Novozyme 435 Proteins 0.000 claims abstract description 4
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 26
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- 239000000243 solution Substances 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 7
- 238000006243 chemical reaction Methods 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 238000004440 column chromatography Methods 0.000 claims description 2
- 239000011259 mixed solution Substances 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 claims 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 claims 1
- -1 be dried Substances 0.000 claims 1
- 239000012141 concentrate Substances 0.000 claims 1
- 238000006073 displacement reaction Methods 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 230000007062 hydrolysis Effects 0.000 claims 1
- 238000006460 hydrolysis reaction Methods 0.000 claims 1
- 229960002510 mandelic acid Drugs 0.000 claims 1
- 239000000463 material Substances 0.000 claims 1
- 238000010792 warming Methods 0.000 claims 1
- 230000006340 racemization Effects 0.000 abstract description 7
- DQVWXLRNCXQVKH-SECBINFHSA-N acetyl (2r)-2-hydroxy-2-phenylacetate Chemical compound CC(=O)OC(=O)[C@H](O)C1=CC=CC=C1 DQVWXLRNCXQVKH-SECBINFHSA-N 0.000 abstract description 3
- 125000002252 acyl group Chemical group 0.000 abstract description 2
- BDXKFBMUZNFKQH-SNVBAGLBSA-N (3R)-3-naphthalen-1-ylbutanamide Chemical compound C1(=CC=CC2=CC=CC=C12)[C@H](C)CC(=O)N BDXKFBMUZNFKQH-SNVBAGLBSA-N 0.000 abstract 1
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 abstract 1
- 150000001408 amides Chemical class 0.000 abstract 1
- 238000004519 manufacturing process Methods 0.000 abstract 1
- 238000000746 purification Methods 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000000047 product Substances 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 238000011914 asymmetric synthesis Methods 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- HZFBJELVFKLVAN-GDNBJRDFSA-N CC(/C(/c1ccccc1C)=C/CC(C)=C)N Chemical compound CC(/C(/c1ccccc1C)=C/CC(C)=C)N HZFBJELVFKLVAN-GDNBJRDFSA-N 0.000 description 1
- 0 C[C@@](C*=*)C=C(C=CC=C1)C1=CC=CC=CC Chemical compound C[C@@](C*=*)C=C(C=CC=C1)C1=CC=CC=CC 0.000 description 1
- XGBIXNJYJYWQSQ-ZCFIWIBFSA-N C[C@@]1(C2CC2)NC1 Chemical compound C[C@@]1(C2CC2)NC1 XGBIXNJYJYWQSQ-ZCFIWIBFSA-N 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- ZUQXNLCTJRBSAC-UHFFFAOYSA-N acetic acid;naphthalen-1-ol Chemical compound CC(O)=O.C1=CC=C2C(O)=CC=CC2=C1 ZUQXNLCTJRBSAC-UHFFFAOYSA-N 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 1
- 150000002314 glycerols Chemical class 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- UFWIBTONFRDIAS-UHFFFAOYSA-N naphthalene-acid Natural products C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
Landscapes
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明涉及一种动态动力学拆分制备R‑1‑萘乙胺的方法。以1‑萘乙胺为原料，Novozym 435为拆分催化剂，D‑(‑)‑O‑乙酰基扁桃酸为酰基供体，KT‑02（镍型催剂）为消旋催化剂，在高压釜中通入氢气进行反应，1‑萘乙胺转化完全得(R)‑(1‑(1‑萘基)乙基)乙酰胺（ee值99%）；酰胺纯化后进行酸解得R‑1‑萘乙胺盐，盐再通过碱化、萃取、干燥、浓缩等操作得R‑1‑萘乙胺，整个步骤产品收率和ee值均可达90%以上。本发明具备消旋催化剂廉价易得、原料利用完全、产品收率好等特点。在R‑1‑萘乙胺的生产制备中，具有极大的指导和应用价值。
Description
技术领域
本发明涉及一种光学纯手性胺的拆分制备方法，尤其涉及光学纯R-1-萘乙胺的拆分及制备方法。
背景技术
光学纯的手性胺是一种非常重要的药物中间体。目前获得光学纯的手性胺主要通过以下几种方法：酶拆分(Indian J.Chem.Sect.B 2005,44,1312-1316；J.Org.Chem.1997,62,3488-3495)；化学拆分：用手性α-羟基萘乙酸(US6342636；Tetrahedron:asymmetry,1998,9,2219-2212)或保护的手性甘油醇衍生物拆分(Tetrahedron:asymmetry,1996,7,1117-1122；Tetrahedron:asymmetry,2002,13,2277-2282)；通过相应的醛经不对称合成得到(WO2004/110976；J.Org.Chem.1992,57,1237-1241)。
在现有的方法中，不对称合成法成本高且经常难得到光学纯度高的产物；化学拆分法及酶法动力学拆分存在原料的利用率低的缺点，最多只有50％；而现报道的酶法动态动力学拆分法中，所使用的消旋催化剂通常是一些钌、铑等贵金属的复合物，这些消旋催化剂成本极高，且拆分制备过程中使用这些消旋催化剂时，虽然实现高转化率但是产品难以获得高的光学纯度。
发明内容
本发明要解决的技术问题是找到一种价格低廉的消旋催化剂，同时实现R-1-萘乙胺在拆分制备过种中的高收率以及高光学纯度。
为了解决上述问题，本发明提供了一种光学纯R-1-萘乙胺的拆分制备方法：1)在高压釜中，以甲苯为溶剂，按摩尔比1:1.0～2.0的比例加入原料1-萘乙胺和酰基供体D-(-)-O-乙酰基扁桃酸，最后再按原料1-萘乙胺质量分数1％-10％的比例加入脂肪酶novozym 435和KT-02，高压釜密封进行氮气置换后，通入氢气至压力0.1-1.0MPa并升温至40-70℃反应18小时，即可将1-萘乙胺完全转化为(R)-(N-(1-萘基)乙基)乙酰胺，且产物ee值可达99％；反应结束后，将溶液进行浓缩，柱层析，得纯(R)-(N-(1-萘基)乙基)乙酰胺，2)将步骤1中制得的((R)-(N-(1-萘基)乙基)乙酰胺溶解在10倍体积比的醇与酸液(醇与酸按体积比1:1配制)的混合溶液中，然后加热回流反应24小时，(R)-(N-(1-萘基)乙基)乙酰胺完全水解得R-1-萘乙胺盐；3)将步骤2所得R-1-萘乙胺盐进行碱化处理，然后通过有机溶剂萃取、干燥、浓缩即可得到光学纯的R-1-萘乙胺，最终整个步骤产品收率可达90％以上，且产品纯度为99％。
本发明在制备光学纯R-1-萘乙胺过程中使用的消旋催化剂为KT-02具有低廉易得的特点，且最终制备得到的光学纯R-1-萘乙胺收率好，光学纯度高。
具体实施方式
1)拆分制备(R)-(N-(1-萘基)乙基)乙酰胺
1000mL的高压釜中加入500mL甲苯作为溶剂，依次加入85.5g1-萘乙胺、106.7g D-(-)-O-乙酰基扁桃酸，5g脂肪酶novozym 435和7gKT-02，加入完毕后，密封高压釜后用氮气将釜内空气进行置换，然后往高压釜内通入氢气至压力1.0MP，开启搅拌，并升温至60℃进行反应；20小时后，取样检测，1-萘乙胺消失完全转化为(R)-(N-(1-萘基)乙基)乙酰胺，且产物ee值达99％；反应结束后，将溶液进行浓缩，然后用体积比为10:1的正已烷与乙醇混合溶剂进行柱层析，得纯(R)-(N-(1-萘基)乙基)乙酰胺101.6g，收率为95.4％。
2)酸解获得R-1-萘乙胺盐
将上步中制得的(R)-(N-(1-萘基)乙基)乙酰胺53g加入到500ml的乙醇和浓盐酸以体积比1:1混合的溶液中，然后加热回流，反应24小时后，点板检测(R)-(N-(1-萘基)乙基)乙酰胺完全水解得R-1-萘乙胺盐。
3)碱化获得R-1-萘乙胺
将步骤2所得反应完全的溶液加入500mL的二氯甲烷，然后缓慢滴加氢氧化钠溶液，并进行搅拌，检测溶液PH值至13，停止滴加氢氧化钠溶液，分液，上层水溶液再次用200mL的二氯甲烷萃取3次，将几次萃取得到的二氯甲烷溶液用无水硫酸钠进行干燥、浓缩得R-1-萘乙胺40.4g，收率为94.4％，HPLC检测最终产品的ee值为99.4％。
Claims (1)
1.光学纯R-1-萘乙胺的拆分制备方法其特征在于：1)在高压反应釜中，以甲苯为溶剂，按摩尔比1:1.0-2.0的比例加入原料1-萘乙胺和酰基供体D-(-)-O-乙酰基扁桃酸，然后按原料1-萘乙胺质量分数1％-10％的比例加入脂肪酶novozym 435和镍型催化剂KT-02，高压釜密封进行氮气置换后，通入氢气至压力0.1-1.0MPa并升温至40-70℃反应18小时，即可将1-萘乙胺完全转化为(R)-(N-(1-萘基)乙基)乙酰胺，且产物ee值达99％；反应结束后，将溶液进行浓缩、柱层析，得纯(R)-(N-(1-萘基)乙基)乙酰胺；2)将步骤1中制得的(R)-(N-(1-萘基)乙基)乙酰胺溶解在10倍体积比的以1:1的体积比配制的醇与酸混合溶液中，然后加热回流反应24小时，(R)-(N-(1-萘基)乙基)乙酰胺完全水解得R-1-萘乙胺盐酸盐；3)将步骤2所得R-1-萘乙胺盐酸盐进行碱化处理，然后通过有机溶剂萃取、干燥、浓缩即可得到光学纯的R-1-萘乙胺，最终整个步骤产品收率可达93％以上，且产品纯度为99％；根据所述，其反应方程式如下：
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410399401.9A CN104151171B (zh) | 2014-08-14 | 2014-08-14 | 一种拆分制备光学纯r-1-萘乙胺的方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410399401.9A CN104151171B (zh) | 2014-08-14 | 2014-08-14 | 一种拆分制备光学纯r-1-萘乙胺的方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104151171A CN104151171A (zh) | 2014-11-19 |
| CN104151171B true CN104151171B (zh) | 2016-07-27 |
Family
ID=51876835
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410399401.9A Active CN104151171B (zh) | 2014-08-14 | 2014-08-14 | 一种拆分制备光学纯r-1-萘乙胺的方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104151171B (zh) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105061218B (zh) * | 2015-08-13 | 2017-02-01 | 上海现代制药营销有限公司 | 动态动力学拆分制备(s)‑1‑氨基茚满 |
| CN105063162A (zh) * | 2015-08-18 | 2015-11-18 | 陈永军 | 拆分制备r-6-甲氧基-1-氨基茚满 |
| CN105154513A (zh) * | 2015-08-18 | 2015-12-16 | 陈永军 | 拆分制备r-5-甲基-1-氨基茚满的方法 |
| CN111004236B (zh) * | 2019-12-19 | 2022-04-05 | 卓和药业集团股份有限公司 | 一种wxfl10203614中间体的动态动力学拆分方法 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4983771A (en) * | 1989-09-18 | 1991-01-08 | Hexcel Corporation | Method for resolution of D,L-alpha-phenethylamine with D(-)mandelic acid |
| CN1835909A (zh) * | 2003-06-13 | 2006-09-20 | 艾夫西亚药品有限公司 | 芳胺的制备方法 |
| CN101514163A (zh) * | 2009-04-02 | 2009-08-26 | 广州辉宏生物医药科技有限公司 | 光学纯西布曲明及其衍生盐的制备工艺 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS59110656A (ja) * | 1982-12-15 | 1984-06-26 | Hiroyuki Nohira | 光学活性な１―フェニル―２―（パラ―トリル）エチルアミンの製造方法 |
-
2014
- 2014-08-14 CN CN201410399401.9A patent/CN104151171B/zh active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4983771A (en) * | 1989-09-18 | 1991-01-08 | Hexcel Corporation | Method for resolution of D,L-alpha-phenethylamine with D(-)mandelic acid |
| CN1835909A (zh) * | 2003-06-13 | 2006-09-20 | 艾夫西亚药品有限公司 | 芳胺的制备方法 |
| CN101514163A (zh) * | 2009-04-02 | 2009-08-26 | 广州辉宏生物医药科技有限公司 | 光学纯西布曲明及其衍生盐的制备工艺 |
Non-Patent Citations (4)
| Title |
|---|
| Heterogeneous Raney Nickel and Cobalt Catalysts for Racemization and Dynamic Kinetic Resolution of Amines;Andrei N.Parvulescu等;《Adv.Synth.Catal.》;20071220;第350卷;第113页左栏，第116页表2，第120页右栏倒数第1-2段 * |
| 动态动力学拆分制备(R)-氨基茚满;戴晓庭 等;《有机化学》;20140124;第34卷;第933-937页 * |
| 新型酰基供体用于酶法动力学拆分制备(R)-1-(2-萘基)乙胺的研究;符思敏 等;《有机化学》;20121231;第32卷;第527页，第529页表4 * |
| 用循环拆分法制备手性萘乙胺;胡键 等;《合成化学》;20101231;第18卷(第1期);第62页左栏倒数第2段 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104151171A (zh) | 2014-11-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104151169B (zh) | 一种拆分制备光学纯s-1-苯乙胺的方法 | |
| CN104152525B (zh) | 一种拆分制备光学纯r‑1‑苯乙胺的方法 | |
| CN104151171B (zh) | 一种拆分制备光学纯r-1-萘乙胺的方法 | |
| CN102277392B (zh) | 一种（r）-1-（1-萘基）乙胺的化学酶拆分制备方法 | |
| CN104370755B (zh) | 一种光学活性的3‑氨基丁醇和3‑氨基丁酸的制备方法 | |
| CN104263796B (zh) | 一种r‑1‑四氢萘胺的制备方法 | |
| CN104263797B (zh) | R‑1‑四氢萘胺的制备 | |
| CN104152526B (zh) | 一种拆分制备光学纯r-1-苯乙胺的方法 | |
| CN104263798B (zh) | S-1-四氢萘胺的制备 | |
| CN104276956A (zh) | 一种s-1-四氢萘胺的制备方法 | |
| CN104164470B (zh) | 一种拆分制备光学纯r-1-萘乙胺的方法 | |
| CN104178545B (zh) | 一种拆分制备光学纯s-2-萘乙胺的方法 | |
| CN104152527B (zh) | 一种拆分制备光学纯r-2-萘乙胺的方法 | |
| CN104263801B (zh) | 一种r-2-四氢萘胺的制备方法 | |
| CN104045592A (zh) | 制备5-氟吲哚-2-酮的方法 | |
| CN105063161B (zh) | 一种r-1-氨基茚满的制备方法 | |
| CN104178547B (zh) | 一种拆分制备光学纯s-1-萘乙胺的方法 | |
| CN104152527A (zh) | 一种拆分制备光学纯r-2-萘乙胺的方法 | |
| CN104262169B (zh) | R-2-四氢萘胺的制备 | |
| CN104178546B (zh) | 一种拆分制备光学纯s-1-萘乙胺的方法 | |
| CN104152528B (zh) | 一种拆分制备光学纯r-2-萘乙胺的方法 | |
| CN104263800B (zh) | S-2-四氢萘胺的制备方法 | |
| CN104131062B (zh) | 一种拆分制备光学纯s-1-苯乙胺的方法 | |
| CN105017035A (zh) | 动态动力学拆分制备(s)-6-羟基-1-氨基茚满 | |
| CN105087742B (zh) | 动态动力学拆分制备r-6-羟基-1-氨基茚满 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C41 | Transfer of patent application or patent right or utility model | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20160627 Address after: 237000 Anhui Province, Lu'an City Economic Development Zone West Lu'an gatever PI Biochemical Technology Co. Ltd. Applicant after: Liuan Jianuo Biochemical Technology Co.,Ltd. Address before: 246000 Anhui Province, Anqing City Yingjiang District chengdun northbound No. 20 Lane four Applicant before: Chen Yongjun |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Method for preparing optically pure R-1-naphthylethylamine by splitting Effective date of registration: 20181129 Granted publication date: 20160727 Pledgee: Jinzhai Anhui rural commercial bank Limited by Share Ltd. Pledgor: Liuan Jianuo Biochemical Technology Co.,Ltd. Registration number: 2018340000681 |
|
| PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20211126 Granted publication date: 20160727 Pledgee: Jinzhai Anhui rural commercial bank Limited by Share Ltd. Pledgor: Liuan Jianuo Biochemical Technology Co.,Ltd. Registration number: 2018340000681 |
|
| PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A method for preparing optically pure r-1-naphthalene ethylamine by resolution Effective date of registration: 20211126 Granted publication date: 20160727 Pledgee: Jinzhai Anhui rural commercial bank Limited by Share Ltd. Pledgor: Liuan Jianuo Biochemical Technology Co.,Ltd. Registration number: Y2021980013460 |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
| PC01 | Cancellation of the registration of the contract for pledge of patent right |
Granted publication date: 20160727 Pledgee: Jinzhai Anhui rural commercial bank Limited by Share Ltd. Pledgor: Liuan Jianuo Biochemical Technology Co.,Ltd. Registration number: Y2021980013460 |
|
| PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A method for preparing optically pure R-1-naphthalenethylamine by splitting Granted publication date: 20160727 Pledgee: Jinzhai Anhui rural commercial bank Limited by Share Ltd. Pledgor: Liuan Jianuo Biochemical Technology Co.,Ltd. Registration number: Y2024980060249 |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right |