TWI331605B - A process for the preparation of racemic citalopram diol and/or s- or r-citalopram diols and the use of such diols for the preparation of racemic citalopram, r-citalopram and/or s-citalopram - Google Patents

A process for the preparation of racemic citalopram diol and/or s- or r-citalopram diols and the use of such diols for the preparation of racemic citalopram, r-citalopram and/or s-citalopram Download PDF

Info

Publication number: TWI331605B
Authority: TW; Taiwan
Prior art keywords: diol; acid addition; addition salt; free base; residue
Prior art date: 2002-12-23

Application number

TW092135925A

Other languages

English (en)

Chinese (zh)

Other versions

TW200512202A (en

Inventor

Hans Petersen

Robert Dancer

Brian Christiansen

Rikke Eva Humble

Original Assignee

Lundbeck & Co As H

Priority date (The priority date 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 date listed.)

2002-12-23

Filing date

2003-12-18

Publication date

2010-10-11

2003-12-18 Application filed by Lundbeck & Co As H filed Critical Lundbeck & Co As H

2005-04-01 Publication of TW200512202A publication Critical patent/TW200512202A/zh

2010-10-11 Application granted granted Critical

2010-10-11 Publication of TWI331605B publication Critical patent/TWI331605B/zh

Links

150000002009 diols Chemical class 0.000 title claims description 102
238000000034 method Methods 0.000 title claims description 78
238000002360 preparation method Methods 0.000 title claims description 19
-1 citalopram diol Chemical class 0.000 title claims description 10
229960001653 citalopram Drugs 0.000 title description 9
WSEQXVZVJXJVFP-HXUWFJFHSA-N (R)-citalopram Chemical compound C1([C@@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-HXUWFJFHSA-N 0.000 title description 3
239000002253 acid Substances 0.000 claims description 203
150000003839 salts Chemical class 0.000 claims description 193
239000000203 mixture Substances 0.000 claims description 137
239000012458 free base Substances 0.000 claims description 127
239000002244 precipitate Substances 0.000 claims description 60
LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 58
239000002904 solvent Substances 0.000 claims description 52
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 45
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 42
239000012071 phase Substances 0.000 claims description 39
238000012360 testing method Methods 0.000 claims description 35
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 32
WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 30
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 22
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 20
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 19
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 17
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 14
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
239000000126 substance Substances 0.000 claims description 12
241000218645 Cedrus Species 0.000 claims description 11
239000013078 crystal Substances 0.000 claims description 11
238000000746 purification Methods 0.000 claims description 10
238000004090 dissolution Methods 0.000 claims description 9
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 8
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 8
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 8
238000001704 evaporation Methods 0.000 claims description 8
230000008020 evaporation Effects 0.000 claims description 8
238000002156 mixing Methods 0.000 claims description 8
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 7
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 6
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 6
235000006408 oxalic acid Nutrition 0.000 claims description 6
229930182558 Sterol Natural products 0.000 claims description 5
235000003702 sterols Nutrition 0.000 claims description 5
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
150000001298 alcohols Chemical class 0.000 claims description 4
230000015572 biosynthetic process Effects 0.000 claims description 4
150000002576 ketones Chemical class 0.000 claims description 4
230000001376 precipitating effect Effects 0.000 claims description 4
238000001953 recrystallisation Methods 0.000 claims description 4
240000004808 Saccharomyces cerevisiae Species 0.000 claims description 3
230000002378 acidificating effect Effects 0.000 claims description 3
150000001875 compounds Chemical class 0.000 claims description 3
150000003891 oxalate salts Chemical class 0.000 claims description 3
239000002798 polar solvent Substances 0.000 claims description 3
102100034279 Calcium-binding mitochondrial carrier protein Aralar2 Human genes 0.000 claims description 2
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 claims description 2
UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 claims description 2
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
229910019142 PO4 Inorganic materials 0.000 claims description 2
108010084210 citrin Proteins 0.000 claims description 2
229940098779 methanesulfonic acid Drugs 0.000 claims description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 2
239000010452 phosphate Substances 0.000 claims description 2
150000003432 sterols Chemical class 0.000 claims description 2
235000011149 sulphuric acid Nutrition 0.000 claims description 2
239000008096 xylene Substances 0.000 claims description 2
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims 2
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims 2
230000000977 initiatory effect Effects 0.000 claims 2
238000005191 phase separation Methods 0.000 claims 2
150000001335 aliphatic alkanes Chemical class 0.000 claims 1
230000003113 alkalizing effect Effects 0.000 claims 1
150000004945 aromatic hydrocarbons Chemical class 0.000 claims 1
239000002826 coolant Substances 0.000 claims 1
229960004279 formaldehyde Drugs 0.000 claims 1
230000000887 hydrating effect Effects 0.000 claims 1
239000007791 liquid phase Substances 0.000 claims 1
239000012453 solvate Substances 0.000 claims 1
238000000638 solvent extraction Methods 0.000 claims 1
210000000952 spleen Anatomy 0.000 claims 1
239000000243 solution Substances 0.000 description 33
239000007787 solid Substances 0.000 description 26
239000012452 mother liquor Substances 0.000 description 21
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 18
238000001556 precipitation Methods 0.000 description 15
239000000047 product Substances 0.000 description 15
JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 11
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
239000002585 base Substances 0.000 description 10
238000000926 separation method Methods 0.000 description 10
238000009826 distribution Methods 0.000 description 8
239000007788 liquid Substances 0.000 description 8
238000011084 recovery Methods 0.000 description 7
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
235000011114 ammonium hydroxide Nutrition 0.000 description 6
239000008346 aqueous phase Substances 0.000 description 5
239000007864 aqueous solution Substances 0.000 description 5
238000002425 crystallisation Methods 0.000 description 5
230000008025 crystallization Effects 0.000 description 5
239000000284 extract Substances 0.000 description 5
238000007429 general method Methods 0.000 description 5
229910052943 magnesium sulfate Inorganic materials 0.000 description 5
235000019341 magnesium sulphate Nutrition 0.000 description 5
238000007363 ring formation reaction Methods 0.000 description 5
239000011780 sodium chloride Substances 0.000 description 5
108091006629 SLC13A2 Proteins 0.000 description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
241000218691 Cupressaceae Species 0.000 description 3
238000004458 analytical method Methods 0.000 description 3
DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 3
229960004316 cisplatin Drugs 0.000 description 3
238000001816 cooling Methods 0.000 description 3
230000008030 elimination Effects 0.000 description 3
238000003379 elimination reaction Methods 0.000 description 3
239000012065 filter cake Substances 0.000 description 3
238000001914 filtration Methods 0.000 description 3
238000004519 manufacturing process Methods 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
238000006798 ring closing metathesis reaction Methods 0.000 description 3
PLFFHJWXOGYWPR-HEDMGYOXSA-N (4r)-4-[(3r,3as,5ar,5br,7as,11as,11br,13ar,13bs)-5a,5b,8,8,11a,13b-hexamethyl-1,2,3,3a,4,5,6,7,7a,9,10,11,11b,12,13,13a-hexadecahydrocyclopenta[a]chrysen-3-yl]pentan-1-ol Chemical compound C([C@]1(C)[C@H]2CC[C@H]34)CCC(C)(C)[C@@H]1CC[C@@]2(C)[C@]4(C)CC[C@@H]1[C@]3(C)CC[C@@H]1[C@@H](CCCO)C PLFFHJWXOGYWPR-HEDMGYOXSA-N 0.000 description 2
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
QTANTQQOYSUMLC-UHFFFAOYSA-O Ethidium cation Chemical compound C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 QTANTQQOYSUMLC-UHFFFAOYSA-O 0.000 description 2
206010036790 Productive cough Diseases 0.000 description 2
KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
229920000180 alkyd Polymers 0.000 description 2
239000000935 antidepressant agent Substances 0.000 description 2
238000006243 chemical reaction Methods 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
230000018044 dehydration Effects 0.000 description 2
238000006297 dehydration reaction Methods 0.000 description 2
239000012259 ether extract Substances 0.000 description 2
239000007789 gas Substances 0.000 description 2
150000002334 glycols Chemical class 0.000 description 2
239000000463 material Substances 0.000 description 2
239000012454 non-polar solvent Substances 0.000 description 2
230000003287 optical effect Effects 0.000 description 2
239000008194 pharmaceutical composition Substances 0.000 description 2
229910052707 ruthenium Inorganic materials 0.000 description 2
229910052938 sodium sulfate Inorganic materials 0.000 description 2
235000011152 sodium sulphate Nutrition 0.000 description 2
210000003802 sputum Anatomy 0.000 description 2
208000024794 sputum Diseases 0.000 description 2
238000003756 stirring Methods 0.000 description 2
238000004808 supercritical fluid chromatography Methods 0.000 description 2
DVWYNPADZDHBSJ-UHFFFAOYSA-N 1-methyl-1-(2-methylpropyl)hydrazine Chemical compound CC(C)CN(C)N DVWYNPADZDHBSJ-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
206010012735 Diarrhoea Diseases 0.000 description 1
RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical class S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
241000196324 Embryophyta Species 0.000 description 1
108010068370 Glutens Proteins 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
239000004990 Smectic liquid crystal Substances 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
208000027418 Wounds and injury Diseases 0.000 description 1
230000000996 additive effect Effects 0.000 description 1
150000004703 alkoxides Chemical class 0.000 description 1
230000001430 anti-depressive effect Effects 0.000 description 1
RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
238000001354 calcination Methods 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
238000004296 chiral HPLC Methods 0.000 description 1
238000013375 chromatographic separation Methods 0.000 description 1
230000006378 damage Effects 0.000 description 1
238000010908 decantation Methods 0.000 description 1
238000010612 desalination reaction Methods 0.000 description 1
238000001514 detection method Methods 0.000 description 1
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
210000005069 ears Anatomy 0.000 description 1
229960004341 escitalopram Drugs 0.000 description 1
WSEQXVZVJXJVFP-FQEVSTJZSA-N escitalopram Chemical compound C1([C@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-FQEVSTJZSA-N 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
238000000605 extraction Methods 0.000 description 1
238000000855 fermentation Methods 0.000 description 1
230000004151 fermentation Effects 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
235000021312 gluten Nutrition 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 description 1
229910052739 hydrogen Inorganic materials 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
208000014674 injury Diseases 0.000 description 1
239000013067 intermediate product Substances 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
239000006166 lysate Substances 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
238000010899 nucleation Methods 0.000 description 1
CBFCDTFDPHXCNY-UHFFFAOYSA-N octyldodecane Natural products CCCCCCCCCCCCCCCCCCCC CBFCDTFDPHXCNY-UHFFFAOYSA-N 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000002923 oximes Chemical class 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
229920005862 polyol Polymers 0.000 description 1
150000003077 polyols Chemical class 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
238000005215 recombination Methods 0.000 description 1
230000006798 recombination Effects 0.000 description 1
BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
230000000717 retained effect Effects 0.000 description 1
239000011833 salt mixture Substances 0.000 description 1
239000013049 sediment Substances 0.000 description 1
229940126570 serotonin reuptake inhibitor Drugs 0.000 description 1
239000003772 serotonin uptake inhibitor Substances 0.000 description 1
HIEHAIZHJZLEPQ-UHFFFAOYSA-M sodium;naphthalene-1-sulfonate Chemical compound [Na+].C1=CC=C2C(S(=O)(=O)[O-])=CC=CC2=C1 HIEHAIZHJZLEPQ-UHFFFAOYSA-M 0.000 description 1
239000002689 soil Substances 0.000 description 1
239000011973 solid acid Substances 0.000 description 1
150000003431 steroids Chemical class 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
125000002730 succinyl group Chemical group C(CCC(=O)*)(=O)* 0.000 description 1
239000001117 sulphuric acid Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
150000003505 terpenes Chemical class 0.000 description 1
235000007586 terpenes Nutrition 0.000 description 1
239000012485 toluene extract Substances 0.000 description 1
238000012795 verification Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/32—Separation; Purification; Stabilisation; Use of additives
- C07C253/34—Separation; Purification
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/275—Nitriles; Isonitriles
- A61K31/277—Nitriles; Isonitriles having a ring, e.g. verapamil
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/87—Benzo [c] furans; Hydrogenated benzo [c] furans

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Epidemiology (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

TW092135925A 2002-12-23 2003-12-18 A process for the preparation of racemic citalopram diol and/or s- or r-citalopram diols and the use of such diols for the preparation of racemic citalopram, r-citalopram and/or s-citalopram TWI331605B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
DKPA200202004		2002-12-23

Publications (2)

Publication Number	Publication Date
TW200512202A TW200512202A (en)	2005-04-01
TWI331605B true TWI331605B (en)	2010-10-11

Family

ID=35423357

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
TW092135925A TWI331605B (en)	2002-12-23	2003-12-18	A process for the preparation of racemic citalopram diol and/or s- or r-citalopram diols and the use of such diols for the preparation of racemic citalopram, r-citalopram and/or s-citalopram

Country Status (17)

Country	Link
KR (1)	KR101076640B1 (es)
CN (1)	CN100334071C (es)
AR (1)	AR042655A1 (es)
BR (1)	BR0317629A (es)
DK (1)	DK1581483T3 (es)
EA (1)	EA009061B1 (es)
ES (1)	ES2385975T3 (es)
ME (1)	MEP5708A (es)
MY (1)	MY142404A (es)
PE (1)	PE20050065A1 (es)
PT (1)	PT1581483E (es)
RS (1)	RS52152B (es)
SI (1)	SI1581483T1 (es)
TW (1)	TWI331605B (es)
UA (1)	UA84859C2 (es)
UY (1)	UY28146A1 (es)
ZA (1)	ZA200504715B (es)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
UA95199U (uk)	2014-07-09	2014-12-10		Дозатор з точним дозуванням для сипучих продуктів
CN110590602B (zh) *	2019-09-25	2022-04-05	浙江海森药业股份有限公司	外消旋西酞普兰二醇的拆分精制方法
CN114763329A (zh) *	2021-01-14	2022-07-19	浙江华海药业股份有限公司	一种西酞普兰关键中间体的纯化方法

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB8814057D0 (en) *	1988-06-14	1988-07-20	Lundbeck & Co As H	New enantiomers & their isolation
AR034612A1 (es) *	2001-06-25	2004-03-03	Lundbeck & Co As H	Proceso para la preparacion del citalopram racemico y/o del s- o r-citalopram mediante la separacion de una mezcla de r- y s-citalopram

2003
- 2003-12-18 KR KR1020057011898A patent/KR101076640B1/ko not_active Expired - Fee Related
- 2003-12-18 RS YU20050488A patent/RS52152B/sr unknown
- 2003-12-18 BR BR0317629-0A patent/BR0317629A/pt not_active Application Discontinuation
- 2003-12-18 DK DK03767476.9T patent/DK1581483T3/da active
- 2003-12-18 PT PT03767476T patent/PT1581483E/pt unknown
- 2003-12-18 CN CNB200380107283XA patent/CN100334071C/zh not_active Expired - Lifetime
- 2003-12-18 ES ES03767476T patent/ES2385975T3/es not_active Expired - Lifetime
- 2003-12-18 SI SI200332174T patent/SI1581483T1/sl unknown
- 2003-12-18 EA EA200501042A patent/EA009061B1/ru not_active IP Right Cessation
- 2003-12-18 UA UAA200506921A patent/UA84859C2/ru unknown
- 2003-12-18 ME MEP-57/08A patent/MEP5708A/xx unknown
- 2003-12-18 TW TW092135925A patent/TWI331605B/zh not_active IP Right Cessation
- 2003-12-22 UY UY28146A patent/UY28146A1/es not_active Application Discontinuation
- 2003-12-22 AR ARP030104781A patent/AR042655A1/es unknown
- 2003-12-22 MY MYPI20034948A patent/MY142404A/en unknown
2004
- 2004-01-05 PE PE2004000033A patent/PE20050065A1/es not_active Application Discontinuation
2005
- 2005-06-09 ZA ZA200504715A patent/ZA200504715B/en unknown

Also Published As

Publication number	Publication date
RS20050488A (sr)	2007-06-04
CN100334071C (zh)	2007-08-29
KR101076640B1 (ko)	2011-10-27
ZA200504715B (en)	2006-08-30
EA009061B1 (ru)	2007-10-26
CN1729164A (zh)	2006-02-01
DK1581483T3 (da)	2012-07-23
SI1581483T1 (sl)	2012-09-28
PE20050065A1 (es)	2005-02-18
AR042655A1 (es)	2005-06-29
RS52152B (sr)	2012-08-31
BR0317629A (pt)	2005-11-29
UA84859C2 (ru)	2008-12-10
PT1581483E (pt)	2012-07-24
KR20050093801A (ko)	2005-09-23
UY28146A1 (es)	2004-07-30
ES2385975T3 (es)	2012-08-06
EA200501042A1 (ru)	2005-12-29
ME00034B (me)	2010-02-10
TW200512202A (en)	2005-04-01
MEP5708A (xx)	2010-02-10
MY142404A (en)	2010-11-30

Publication	Publication Date	Title
CN101622225B (zh)	2015-04-15	炔丙基氨基茚分离方法
TWI236473B (en)	2005-07-21	Process for the preparation of racemic citalopram and/or S-or R-citalopram by separation of a mixture of R-and S-citalopram
FR2900655A1 (fr)	2007-11-09	Forme alpha du mesylate d'imatinib et procede de production de celui-ci
CN104379559A (zh)	2015-02-25	新化合物
TW200951102A (en)	2009-12-16	Resolving of 4,5-dimethoxy-1-(methylaminomethyl)-benzocyclobutane
JP4505335B2 (ja)	2010-07-21	ラセミ体シタロプラムジオール（ｒａｃｅｍｉｃｃｉｔａｌｏｐｒａｍｄｉｏｌ）および／またはＳ−もしくはＲ−シタロプラムジオールの製造方法、およびラセミ体シタロプラム、Ｒ−シタロプラムおよび／またはＳ−シタロプラムを製造するために、上記ジオールを使用する方法。
TWI331605B (en)	2010-10-11	A process for the preparation of racemic citalopram diol and/or s- or r-citalopram diols and the use of such diols for the preparation of racemic citalopram, r-citalopram and/or s-citalopram
CH641181A5 (fr)	1984-02-15	Indolo-quinolizidines, procede pour leur preparation et compositions therapeutiques les contenant.
CN101580482A (zh)	2009-11-18	一种重酒石酸盐卡巴拉汀的制备方法和应用
WO2000032554A1 (en)	2000-06-08	Process for the resolution of tramadol
CN101389621A (zh)	2009-03-18	制备一种度洛西汀的中间体(s)-(-)-n,n-二甲基-3-(2-噻吩基)-3-羟基丙胺的方法
US20070117992A1 (en)	2007-05-24	Crystalline citalopram diol intermediate alkali
ES2210128T3 (es)	2004-07-01	Derivados de (2s)-aminoindano, procedimiento para su preparacion y su uso como ligando selectivo de dopamina d3.
EP2513042A2 (en)	2012-10-24	Solid dapoxetine
CN101883486A (zh)	2010-11-10	制备r-棉酚l-苯丙氨醇二烯胺的方法
TWI332939B (en)	2010-11-11	Toremifene crystallization method
CN1046281C (zh)	1999-11-10	药理活性的对映体及其制备方法
JP2008521804A (ja)	2008-06-26	ベンズフェタミンの結晶化方法
WO2003002510A1 (fr)	2003-01-09	Forme cristalline d'une phenylethanolamine, sa preparation et compositions pharmaceutiques la contenant
CN119390591A (zh)	2025-02-07	一种卡巴拉汀中间体的纯化方法
JP2002533457A (ja)	2002-10-08	パロキセチン酢酸塩またはパロキセチンアナログの製造法
JP2002533441A (ja)	2002-10-08	酢酸パロキセチンおよびそのアナログの製造法

Legal Events

Date	Code	Title	Description
2014-07-11	MM4A	Annulment or lapse of patent due to non-payment of fees