CN109627174B - 一种手性盐酸舍曲林的制备方法 - Google Patents
一种手性盐酸舍曲林的制备方法 Download PDFInfo
- Publication number
- CN109627174B CN109627174B CN201811477972.4A CN201811477972A CN109627174B CN 109627174 B CN109627174 B CN 109627174B CN 201811477972 A CN201811477972 A CN 201811477972A CN 109627174 B CN109627174 B CN 109627174B
- Authority
- CN
- China
- Prior art keywords
- sertraline
- mandelic acid
- organic solvent
- mixing
- filtrate
- 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.)
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Links
- 229960003660 sertraline hydrochloride Drugs 0.000 title claims abstract description 69
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- GLQPTZAAUROJMO-UHFFFAOYSA-N 4-(3,4-dimethoxyphenyl)benzaldehyde Chemical compound C1=C(OC)C(OC)=CC=C1C1=CC=C(C=O)C=C1 GLQPTZAAUROJMO-UHFFFAOYSA-N 0.000 title claims abstract description 21
- IWYDHOAUDWTVEP-SSDOTTSWSA-N (R)-mandelic acid Chemical compound OC(=O)[C@H](O)C1=CC=CC=C1 IWYDHOAUDWTVEP-SSDOTTSWSA-N 0.000 claims abstract description 49
- 229960002073 sertraline Drugs 0.000 claims abstract description 46
- 238000000034 method Methods 0.000 claims abstract description 35
- 239000000706 filtrate Substances 0.000 claims abstract description 32
- VGKDLMBJGBXTGI-SJCJKPOMSA-N sertraline Chemical compound C1([C@@H]2CC[C@@H](C3=CC=CC=C32)NC)=CC=C(Cl)C(Cl)=C1 VGKDLMBJGBXTGI-SJCJKPOMSA-N 0.000 claims abstract description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 29
- 238000001816 cooling Methods 0.000 claims abstract description 28
- 239000003960 organic solvent Substances 0.000 claims abstract description 28
- 238000002156 mixing Methods 0.000 claims abstract description 27
- 239000002904 solvent Substances 0.000 claims abstract description 27
- -1 alkali metal salt Chemical class 0.000 claims abstract description 24
- 239000007788 liquid Substances 0.000 claims abstract description 24
- 239000003513 alkali Substances 0.000 claims abstract description 23
- 229910052783 alkali metal Inorganic materials 0.000 claims abstract description 23
- 150000007529 inorganic bases Chemical class 0.000 claims abstract description 21
- 238000000926 separation method Methods 0.000 claims abstract description 20
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 18
- 238000002425 crystallisation Methods 0.000 claims abstract description 18
- 230000008025 crystallization Effects 0.000 claims abstract description 17
- 238000003756 stirring Methods 0.000 claims abstract description 16
- 238000001914 filtration Methods 0.000 claims abstract description 15
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 claims abstract description 15
- 238000001035 drying Methods 0.000 claims abstract description 13
- 239000012043 crude product Substances 0.000 claims abstract description 9
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims abstract description 9
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims abstract description 9
- 238000005406 washing Methods 0.000 claims abstract description 5
- 229910017053 inorganic salt Inorganic materials 0.000 claims abstract description 4
- 239000012046 mixed solvent Substances 0.000 claims abstract description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 44
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 34
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 25
- 239000012065 filter cake Substances 0.000 claims description 19
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 17
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 17
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 14
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 14
- FWDLHTBMGQEUDU-OGFXRTJISA-M sodium;(2r)-2-hydroxy-2-phenylacetate Chemical compound [Na+].[O-]C(=O)[C@H](O)C1=CC=CC=C1 FWDLHTBMGQEUDU-OGFXRTJISA-M 0.000 claims description 13
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 12
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 12
- 239000011736 potassium bicarbonate Substances 0.000 claims description 12
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 12
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 10
- 239000002585 base Substances 0.000 claims description 10
- 238000010438 heat treatment Methods 0.000 claims description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 10
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 230000015572 biosynthetic process Effects 0.000 claims description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 5
- 235000011181 potassium carbonates Nutrition 0.000 claims description 5
- 238000001953 recrystallisation Methods 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 5
- 235000017550 sodium carbonate Nutrition 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 3
- UXIPJZUVTLMZBG-OGFXRTJISA-M potassium (2R)-2-hydroxy-2-phenylacetate Chemical compound [K+].[O-]C(=O)[C@H](O)C1=CC=CC=C1 UXIPJZUVTLMZBG-OGFXRTJISA-M 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- 239000013078 crystal Substances 0.000 claims description 2
- 238000004042 decolorization Methods 0.000 claims description 2
- 229940086066 potassium hydrogencarbonate Drugs 0.000 claims description 2
- 125000003158 alcohol group Chemical group 0.000 claims 3
- 229910052799 carbon Inorganic materials 0.000 claims 2
- 238000011084 recovery Methods 0.000 abstract description 22
- 239000003795 chemical substances by application Substances 0.000 abstract description 5
- 238000009776 industrial production Methods 0.000 abstract description 2
- 239000012467 final product Substances 0.000 abstract 1
- 239000000047 product Substances 0.000 description 17
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 238000001514 detection method Methods 0.000 description 9
- 238000010494 dissociation reaction Methods 0.000 description 8
- 230000005593 dissociations Effects 0.000 description 8
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000010981 drying operation Methods 0.000 description 4
- 235000011121 sodium hydroxide Nutrition 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000001430 anti-depressive effect Effects 0.000 description 2
- 239000000935 antidepressant agent Substances 0.000 description 2
- 229940005513 antidepressants Drugs 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 229960003975 potassium Drugs 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 230000006340 racemization Effects 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- CMQCNTNASCDNGR-UHFFFAOYSA-N toluene;hydrate Chemical compound O.CC1=CC=CC=C1 CMQCNTNASCDNGR-UHFFFAOYSA-N 0.000 description 2
- VGKDLMBJGBXTGI-YVEFUNNKSA-N (1r,4s)-4-(3,4-dichlorophenyl)-n-methyl-1,2,3,4-tetrahydronaphthalen-1-amine Chemical group C1([C@@H]2CC[C@H](C3=CC=CC=C32)NC)=CC=C(Cl)C(Cl)=C1 VGKDLMBJGBXTGI-YVEFUNNKSA-N 0.000 description 1
- 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 description 1
- IWYDHOAUDWTVEP-SSDOTTSWSA-M (R)-mandelate Chemical compound [O-]C(=O)[C@H](O)C1=CC=CC=C1 IWYDHOAUDWTVEP-SSDOTTSWSA-M 0.000 description 1
- VGKDLMBJGBXTGI-UHFFFAOYSA-N 4-(3,4-dichlorophenyl)-n-methyl-1,2,3,4-tetrahydronaphthalen-1-amine Chemical compound C12=CC=CC=C2C(NC)CCC1C1=CC=C(Cl)C(Cl)=C1 VGKDLMBJGBXTGI-UHFFFAOYSA-N 0.000 description 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 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- YDVNLQGCLLPHAH-UHFFFAOYSA-N dichloromethane;hydrate Chemical compound O.ClCCl YDVNLQGCLLPHAH-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- MHYCRLGKOZWVEF-UHFFFAOYSA-N ethyl acetate;hydrate Chemical compound O.CCOC(C)=O MHYCRLGKOZWVEF-UHFFFAOYSA-N 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- JEGUKCSWCFPDGT-UHFFFAOYSA-N h2o hydrate Chemical compound O.O JEGUKCSWCFPDGT-UHFFFAOYSA-N 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 230000036632 reaction speed Effects 0.000 description 1
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 1
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- FWDLHTBMGQEUDU-UHFFFAOYSA-M sodium;2-hydroxy-2-phenylacetate Chemical compound [Na+].[O-]C(=O)C(O)C1=CC=CC=C1 FWDLHTBMGQEUDU-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/33—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C211/39—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of rings other than six-membered aromatic rings of an unsaturated carbon skeleton
- C07C211/41—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of rings other than six-membered aromatic rings of an unsaturated carbon skeleton containing condensed ring systems
- C07C211/42—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of rings other than six-membered aromatic rings of an unsaturated carbon skeleton containing condensed ring systems with six-membered aromatic rings being part of the condensed ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/41—Preparation of salts of carboxylic acids
- C07C51/412—Preparation of salts of carboxylic acids by conversion of the acids, their salts, esters or anhydrides with the same carboxylic acid part
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
Claims (15)
Priority Applications (1)
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CN201811477972.4A CN109627174B (zh) | 2018-12-05 | 2018-12-05 | 一种手性盐酸舍曲林的制备方法 |
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CN201811477972.4A CN109627174B (zh) | 2018-12-05 | 2018-12-05 | 一种手性盐酸舍曲林的制备方法 |
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CN109627174A CN109627174A (zh) | 2019-04-16 |
CN109627174B true CN109627174B (zh) | 2021-11-12 |
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Families Citing this family (1)
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CN111763150B (zh) * | 2019-12-27 | 2024-03-08 | 上虞京新药业有限公司 | 一种手性盐酸舍曲林的制备方法 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2000297066A (ja) * | 1999-04-12 | 2000-10-24 | Yamakawa Yakuhin Kogyo Kk | 光学活性α−メチルベンジルアミンの製造方法 |
CN103450008A (zh) * | 2013-09-02 | 2013-12-18 | 江苏宝众宝达药业有限公司 | 一种从废水中回收扁桃酸的方法 |
CN103524354A (zh) * | 2013-10-23 | 2014-01-22 | 山东鲁药制药有限公司 | 一种盐酸舍曲林的制备方法 |
CN103570555A (zh) * | 2013-10-14 | 2014-02-12 | 浙江工业大学 | 一种手性盐酸舍曲林的制备方法 |
-
2018
- 2018-12-05 CN CN201811477972.4A patent/CN109627174B/zh active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2000297066A (ja) * | 1999-04-12 | 2000-10-24 | Yamakawa Yakuhin Kogyo Kk | 光学活性α−メチルベンジルアミンの製造方法 |
CN103450008A (zh) * | 2013-09-02 | 2013-12-18 | 江苏宝众宝达药业有限公司 | 一种从废水中回收扁桃酸的方法 |
CN103570555A (zh) * | 2013-10-14 | 2014-02-12 | 浙江工业大学 | 一种手性盐酸舍曲林的制备方法 |
CN103524354A (zh) * | 2013-10-23 | 2014-01-22 | 山东鲁药制药有限公司 | 一种盐酸舍曲林的制备方法 |
Non-Patent Citations (1)
Title |
---|
Resolution of methyl 2-amino-2,4-dideoxy-β-D- and -L-threo-pentopyranoside. Determination of their absolute configuration;Genevieve Anker等;《Carbohydrate Research》;19871231;第159卷(第1期);第159-164页 * |
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Address after: 312369 No.31, Weisan Road, Shangyu economic and Technological Development Zone, Hangzhou Bay, Shaoxing City, Zhejiang Province Patentee after: Shaoxing Jingxin Pharmaceutical Co.,Ltd. Country or region after: China Patentee after: SHANGHAI JINGXIN BIOLOGICAL MEDICAL Co.,Ltd. Address before: 312500 No. 31, Weisan Road, Shangyu economic and Technological Development Zone, Hangzhou Bay, Shaoxing City, Zhejiang Province Patentee before: SHANGYU JINGXIN PHARMACEUTICAL Co.,Ltd. Country or region before: China Patentee before: SHANGHAI JINGXIN BIOLOGICAL MEDICAL Co.,Ltd. |