CA1320732C - Procede pour la preparation de l'acide 2-(2-{4-¬4-chlorophenyl)-phenylmethyl|-1-piperazinyl} ethyxy)-acetique et de ses dichlorures - Google Patents

Procede pour la preparation de l'acide 2-(2-{4-¬4-chlorophenyl)-phenylmethyl|-1-piperazinyl} ethyxy)-acetique et de ses dichlorures

Info

Publication number: CA1320732C
Authority: CA; Canada
Prior art keywords: chlorophenyl; alkali metal; phenylmethyl; piperazinyl; reaction
Prior art date: 1988-11-23
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 - Fee Related

Application number

CA000614708A

Other languages

English (en)

Inventor

Guy Bodson

Eric Cossement

Jean Gobert

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

UCB SA

Original Assignee

UCB SA

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.)

1988-11-23

Filing date

1989-09-29

Publication date

1993-07-27

1989-09-29 Application filed by UCB SA filed Critical UCB SA

1993-07-27 Application granted granted Critical

1993-07-27 Publication of CA1320732C publication Critical patent/CA1320732C/fr

2010-07-27 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

238000000034 method Methods 0.000 title claims abstract description 24
238000002360 preparation method Methods 0.000 title claims abstract description 5
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 title description 21
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 title description 9
229910052783 alkali metal Inorganic materials 0.000 claims abstract description 26
150000001340 alkali metals Chemical class 0.000 claims abstract description 22
239000002253 acid Substances 0.000 claims abstract description 13
ZKLPARSLTMPFCP-UHFFFAOYSA-N Cetirizine Chemical compound C1CN(CCOCC(=O)O)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZKLPARSLTMPFCP-UHFFFAOYSA-N 0.000 claims abstract description 8
-1 alkali metal salt Chemical class 0.000 claims abstract description 5
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 16
238000006243 chemical reaction Methods 0.000 claims description 15
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical group [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 9
ZJQSBXXYLQGZBR-UHFFFAOYSA-N 2-[4-[(4-chlorophenyl)-phenylmethyl]piperazin-1-yl]ethanol Chemical compound C1CN(CCO)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZJQSBXXYLQGZBR-UHFFFAOYSA-N 0.000 claims description 8
239000012429 reaction media Substances 0.000 claims description 6
239000002904 solvent Substances 0.000 claims description 5
150000003839 salts Chemical class 0.000 claims description 3
230000003247 decreasing effect Effects 0.000 claims 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 9
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 11
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
239000011541 reaction mixture Substances 0.000 description 8
FDRCDNZGSXJAFP-UHFFFAOYSA-M sodium chloroacetate Chemical compound [Na+].[O-]C(=O)CCl FDRCDNZGSXJAFP-UHFFFAOYSA-M 0.000 description 8
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
230000015572 biosynthetic process Effects 0.000 description 6
239000000203 mixture Substances 0.000 description 6
239000000047 product Substances 0.000 description 6
238000003786 synthesis reaction Methods 0.000 description 6
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 5
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
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 3
229960001803 cetirizine Drugs 0.000 description 3
UZKBSZSTDQSMDR-UHFFFAOYSA-N 1-[(4-chlorophenyl)-phenylmethyl]piperazine Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC=CC=1)N1CCNCC1 UZKBSZSTDQSMDR-UHFFFAOYSA-N 0.000 description 2
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
SZIFAVKTNFCBPC-UHFFFAOYSA-N 2-chloroethanol Chemical compound OCCCl SZIFAVKTNFCBPC-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
PGLIUCLTXOYQMV-UHFFFAOYSA-N Cetirizine hydrochloride Chemical compound Cl.Cl.C1CN(CCOCC(=O)O)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 PGLIUCLTXOYQMV-UHFFFAOYSA-N 0.000 description 2
206010020751 Hypersensitivity Diseases 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
208000026935 allergic disease Diseases 0.000 description 2
230000007815 allergy Effects 0.000 description 2
238000004821 distillation Methods 0.000 description 2
230000000694 effects Effects 0.000 description 2
238000000605 extraction Methods 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
150000007529 inorganic bases Chemical class 0.000 description 2
239000012299 nitrogen atmosphere Substances 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
239000011591 potassium Substances 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
239000000376 reactant Substances 0.000 description 2
238000004064 recycling Methods 0.000 description 2
238000010992 reflux Methods 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000011734 sodium Substances 0.000 description 2
238000003756 stirring Methods 0.000 description 2
239000000126 substance Substances 0.000 description 2
DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
ALKWTKGPKKAZMN-UHFFFAOYSA-N 1-chloro-4-[chloro(phenyl)methyl]benzene Chemical compound C=1C=C(Cl)C=CC=1C(Cl)C1=CC=CC=C1 ALKWTKGPKKAZMN-UHFFFAOYSA-N 0.000 description 1
WFCSWCVEJLETKA-UHFFFAOYSA-N 2-piperazin-1-ylethanol Chemical compound OCCN1CCNCC1 WFCSWCVEJLETKA-UHFFFAOYSA-N 0.000 description 1
206010010744 Conjunctivitis allergic Diseases 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
208000003251 Pruritus Diseases 0.000 description 1
206010039085 Rhinitis allergic Diseases 0.000 description 1
206010041349 Somnolence Diseases 0.000 description 1
208000024780 Urticaria Diseases 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
208000002205 allergic conjunctivitis Diseases 0.000 description 1
230000000172 allergic effect Effects 0.000 description 1
201000010105 allergic rhinitis Diseases 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
239000003849 aromatic solvent Substances 0.000 description 1
208000024998 atopic conjunctivitis Diseases 0.000 description 1
208000010668 atopic eczema Diseases 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
239000013078 crystal Substances 0.000 description 1
238000000113 differential scanning calorimetry Methods 0.000 description 1
239000003814 drug Substances 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
RDFIZBYHUOHTQI-UHFFFAOYSA-N methyl 2-(2-chloroethoxy)acetate Chemical compound COC(=O)COCCCl RDFIZBYHUOHTQI-UHFFFAOYSA-N 0.000 description 1
BYCHNMFDSQCCDD-UHFFFAOYSA-N methyl 2-[2-[4-[(4-chlorophenyl)-phenylmethyl]piperazin-1-yl]ethoxy]acetate Chemical compound C1CN(CCOCC(=O)OC)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 BYCHNMFDSQCCDD-UHFFFAOYSA-N 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
150000007530 organic bases Chemical group 0.000 description 1
239000012074 organic phase 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
229910000027 potassium carbonate Inorganic materials 0.000 description 1
230000009257 reactivity Effects 0.000 description 1
CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
239000007787 solid Substances 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
239000008096 xylene Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

CA000614708A 1988-11-23 1989-09-29 Procede pour la preparation de l'acide 2-(2-{4-¬4-chlorophenyl)-phenylmethyl|-1-piperazinyl} ethyxy)-acetique et de ses dichlorures Expired - Fee Related CA1320732C (fr)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GB888827390A GB8827390D0 (en)	1988-11-23	1988-11-23	Process for preparation of 2-(2-(4-((4-chlorophenyl)phenylmethyl)-1-pipera-zinyl)ethoxy)-acetic acid & its dihydrochloride
GB8827390		1988-11-23

Publications (1)

Publication Number	Publication Date
CA1320732C true CA1320732C (fr)	1993-07-27

Family

ID=10647346

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000614708A Expired - Fee Related CA1320732C (fr)	1988-11-23	1989-09-29	Procede pour la preparation de l'acide 2-(2-{4-¬4-chlorophenyl)-phenylmethyl\|-1-piperazinyl} ethyxy)-acetique et de ses dichlorures

Country Status (17)

Country	Link
KR (1)	KR970009727B1 (fr)
AT (1)	AT398970B (fr)
CA (1)	CA1320732C (fr)
CY (1)	CY1696A (fr)
DK (1)	DK174289B1 (fr)
ES (1)	ES2018967A6 (fr)
FI (1)	FI91861C (fr)
GB (2)	GB8827390D0 (fr)
GR (1)	GR1000576B (fr)
HK (1)	HK45493A (fr)
HU (1)	HU208002B (fr)
NO (1)	NO172287C (fr)
PH (1)	PH26334A (fr)
PL (1)	PL161374B1 (fr)
PT (1)	PT92363B (fr)
RU (1)	RU1838306C (fr)
SG (1)	SG12793G (fr)

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ES2128556T3 (es) *	1992-09-24	1999-05-16	Sepracor Inc	Tratamiento transdermico de la urticaria usando (+)-cetirizina opticamente pura.
JPH08501561A (ja) *	1992-09-24	1996-02-20	セプラコア，インコーポレイテッド	（−）セチリジンを用いたアレルギー疾患の治療のための組成物
BE1010095A3 (fr) *	1996-04-10	1997-12-02	Ucb Sa	Procede de preparation de l'acide 2-[2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl] ethoxy]-acetique et de ses sels.
BE1010094A3 (fr) *	1996-04-10	1997-12-02	Ucb Sa	Nouveaux [2-(1-piperazinyl)ethoxy] methyle substitues.
CA2180993A1 (fr) *	1996-07-11	1998-01-12	Yong Tao	Methodes pour la preparation de cetirizine
EP0919550A1 (fr)	1997-11-26	1999-06-02	Ucb, S.A.	Formes pseudopolymorphiques de l'acide 2-2-4-bis(4-fluorophényl)méthyl -1-pipérazinyl-éthoxy acétique dihydrochloride
IL124195A (en) *	1998-04-23	2000-08-31	Chemagis Ltd	Process for the preparation of esters of 2-¬4-¬4-chlorophenyl¾phenylmethyl¾-1-piperazinyl¬ethoxy¾acetic acid
DK176706B1 (da) *	1999-03-04	2009-03-30	Sandoz As	Fremgangsmåde til fremstilling af 2-{2-[4-(diphenylmethyl)-1-piperazinyl]ethoxy}-eddikesyre-forbindelser eller salte deraf
US6265579B1 (en) *	1999-10-29	2001-07-24	Salsbury Chemicals, Inc.	Process for preparing piperazine-substituted aliphatic carboxylates
US7199241B1 (en)	2001-05-29	2007-04-03	Ucb, S.A.	Process for preparing (S) and (R)-2-[4-(4-chlorobenzhydryl)piperazin-1-yl]-ethoxyacetamide
US6977301B1 (en)	2001-05-29	2005-12-20	Ucb, S.A.	Process for preparing (S) and (R)—2-[4-(4-chlorobenzhydryl)piperazin-1-yl]-ethoxyacetamide
WO2003104211A2 (fr) *	2002-06-05	2003-12-18	Dr. Reddy's Laboratories Limited	Dichlorhydrate cristallin d'acide acetique [2-[4-[(4-chlorophenyl)-phenyl methyl]-1-piperazinyl] ethoxy]
EP1590323A2 (fr)	2003-01-23	2005-11-02	Ucb Farchim, S.A.	Nouveaux derives de piperazine et leur utilisation comme intermediaires de synthese
WO2004103982A1 (fr) *	2003-05-21	2004-12-02	Wockhardt Limited	Monochlorhydrate d'acide 2-[2-[4-[(4-chlorophenyl) phenylmethyl]-1-piperazinyl]ethoxy]acetique utile comme compose anti-allergenique et son procede de production
US20110172425A1 (en)	2008-09-17	2011-07-14	Calyx Chemicals And Pharmaceuticals Pvt. Ltd.	Novel water based process for the preparation of substituted diphenylmethyl piperazines
KR101418404B1 (ko)	2012-01-06	2014-07-10	한미약품 주식회사	레보세티리진 또는 이의 약학적으로 허용가능한 염 및 몬테루카스트 또는 이의 약학적으로 허용가능한 염을 함유하는 안정한 경구투여용 약학 제제
KR102226833B1 (ko)	2013-06-28	2021-03-12	한미약품 주식회사	레보세티리진 및 몬테루카스트를 포함하는 안정성이 개선된 복합 과립 제형

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB817231A (en) *	1956-01-27	1959-07-29	Henri Morren	New derivatives of n-mono-benzhydryl-piperazine and process for the preparation thereof
US3090725A (en) *	1960-02-29	1963-05-21	Burroughs Wellcome Co	Phosphorylated quaternary ammonium compounds of improved oral absorption
FI75816C (fi) *	1981-02-06	1988-08-08	Ucb Sa	Foerfarande foer framstaellning av terapeutiskt aktiv 2-/4-(difenylmetyl)-1-piperazinyl/-aettiksyror eller dess amid.

1988
- 1988-11-23 GB GB888827390A patent/GB8827390D0/en active Pending
1989
- 1989-09-29 CA CA000614708A patent/CA1320732C/fr not_active Expired - Fee Related
- 1989-11-20 GR GR890100771A patent/GR1000576B/el not_active IP Right Cessation
- 1989-11-21 PT PT92363A patent/PT92363B/pt not_active IP Right Cessation
- 1989-11-21 GB GB8926242A patent/GB2225320B/en not_active Expired - Lifetime
- 1989-11-22 DK DK198905865A patent/DK174289B1/da not_active IP Right Cessation
- 1989-11-22 PL PL1989282411A patent/PL161374B1/pl unknown
- 1989-11-22 FI FI895563A patent/FI91861C/fi not_active IP Right Cessation
- 1989-11-22 AT AT0266489A patent/AT398970B/de not_active IP Right Cessation
- 1989-11-22 NO NO894650A patent/NO172287C/no not_active IP Right Cessation
- 1989-11-22 HU HU896130A patent/HU208002B/hu not_active IP Right Cessation
- 1989-11-22 ES ES8903974A patent/ES2018967A6/es not_active Expired - Lifetime
- 1989-11-22 RU SU894742406A patent/RU1838306C/ru active
- 1989-11-23 PH PH39569A patent/PH26334A/en unknown
- 1989-11-23 KR KR1019890017039A patent/KR970009727B1/ko not_active Expired - Fee Related
1993
- 1993-02-06 SG SG127/93A patent/SG12793G/en unknown
- 1993-05-13 HK HK454/93A patent/HK45493A/xx not_active IP Right Cessation
1994
- 1994-01-14 CY CY160694A patent/CY1696A/en unknown

Also Published As

Publication number	Publication date
GB2225320A (en)	1990-05-30
PT92363A (pt)	1990-05-31
FI895563A0 (fi)	1989-11-22
PT92363B (pt)	1995-07-18
HU896130D0 (en)	1990-02-28
CY1696A (en)	1994-01-14
GR890100771A (en)	1990-12-31
HK45493A (en)	1993-05-21
NO894650D0 (no)	1989-11-22
GB8827390D0 (en)	1988-12-29
FI91861B (fi)	1994-05-13
ATA266489A (de)	1994-07-15
AT398970B (de)	1995-02-27
DK586589D0 (da)	1989-11-22
RU1838306C (ru)	1993-08-30
PH26334A (en)	1992-04-29
GR1000576B (el)	1992-08-26
PL161374B1 (pl)	1993-06-30
FI91861C (fi)	1994-08-25
NO172287B (no)	1993-03-22
GB8926242D0 (en)	1990-01-10
KR900007824A (ko)	1990-06-02
GB2225320B (en)	1992-09-02
SG12793G (en)	1993-04-16
ES2018967A6 (es)	1991-05-16
HUT53626A (en)	1990-11-28
HU208002B (en)	1993-07-28
DK174289B1 (da)	2002-11-18
KR970009727B1 (ko)	1997-06-17
NO894650L (no)	1990-05-25
NO172287C (no)	1993-06-30
DK586589A (da)	1990-05-24

Legal Events

Date	Code	Title	Description
2008-07-28	MKLA	Lapsed

Publication	Publication Date	Title
CA1317300C (fr)	1993-05-04	Procede pour la preparation d'acide 2-(2-¬4-¬(4-chlorophenyl)phenylmethyl\|-1-piperazinyl\| ethoxy) acetique et de son dichlorhydrate
CY1696A (en)	1994-01-14	Process for the preparation of 2-(2-(-4((4-chlorophenyl)phenylmethyl)- 1-piperazinyl)ethoxy)-acetic acid and its dihydrochloride
AU2004309280B2 (en)	2007-10-04	Benzene compounds disubstituted with cyclic groups at the 1- and 2-positions
NO155805B (no)	1987-02-23	Analogifremgangsmaate for fremstilling av terapeutisk virksomme 2-(4-(difenylmethyl)-1-piperazinyl)-eddiksyrer og deres amider og ikke-toksiske salter.
US2683742A (en)	1954-07-13	Nu, nu-disubstituted omega-arylmethoxy-omega-arylalkylamine derivatives
EP0192849B1 (fr)	1988-08-31	Procédé de préparation de composés d'acide 2-(4-hydroxy-phénoxy)-propionique optiquement actifs
SU453836A3 (ru)	1974-12-15	Способ получения производных 3-бензилпиридина или их солей
US2966518A (en)	1960-12-27	Process of producing nitrtogen-containing chemical compounds
EP1971585B1 (fr)	2011-03-09	Procede de preparation d'un intermediaire pharmaceutique
EP0295218B1 (fr)	1992-07-22	Procédé de préparation de 2,4-diamino-6-(1-pipéridinyl)-pyrimidine N-oxyde
NO126914B (fr)	1973-04-09
NO143902B (no)	1981-01-26	Fenyl-lavere alkanoylaminer for bruk til fremstilling av terapeutisk virksomme fenyl-lavere-alkylaminer
US3654271A (en)	1972-04-04	Process for preparing simple and substituted morpholines
CN110950818B (zh)	2021-12-28	顺式-2,6-二甲基吗啉的纯化方法
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