NO311352B1 - Ny fremgangsmåte for fremstilling av metoprolol - Google Patents

Ny fremgangsmåte for fremstilling av metoprolol Download PDF

Info

Publication number: NO311352B1
Authority: NO; Norway
Prior art keywords: metoprolol; methoxyethyl; epichlorohydrin; base; resulting
Prior art date: 1996-11-20

Application number

NO19992401A

Other languages

English (en)

Norwegian (no)

Other versions

NO992401D0 (no

NO992401L (no

Inventor

Sven Palmer

Michael Sidenqvist

Original Assignee

Astrazeneca Ab

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.)

1996-11-20

Filing date

1999-05-19

Publication date

2001-11-19

1999-05-19 Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab

1999-05-19 Publication of NO992401D0 publication Critical patent/NO992401D0/no

1999-07-13 Publication of NO992401L publication Critical patent/NO992401L/no

2001-11-19 Publication of NO311352B1 publication Critical patent/NO311352B1/no

Links

IUBSYMUCCVWXPE-UHFFFAOYSA-N metoprolol Chemical compound COCCC1=CC=C(OCC(O)CNC(C)C)C=C1 IUBSYMUCCVWXPE-UHFFFAOYSA-N 0.000 title claims abstract description 25
229960002237 metoprolol Drugs 0.000 title claims abstract description 24
238000000034 method Methods 0.000 title claims abstract description 18
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 11
239000002904 solvent Substances 0.000 claims abstract description 7
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 11
238000006243 chemical reaction Methods 0.000 claims description 10
BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 claims description 9
JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 claims description 7
FAYGEALAEQKPDI-UHFFFAOYSA-N 4-(2-methoxyethyl)phenol Chemical compound COCCC1=CC=C(O)C=C1 FAYGEALAEQKPDI-UHFFFAOYSA-N 0.000 claims description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-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 5
238000004821 distillation Methods 0.000 claims description 5
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 claims description 4
UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 claims description 4
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 3
DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 claims description 2
FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims description 2
239000002934 diuretic Substances 0.000 claims 2
239000000825 pharmaceutical preparation Substances 0.000 claims 2
JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical group C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 claims 1
RGHAZVBIOOEVQX-UHFFFAOYSA-N Metoprolol succinate Chemical compound OC(=O)CCC(O)=O.COCCC1=CC=C(OCC(O)CNC(C)C)C=C1.COCCC1=CC=C(OCC(O)CNC(C)C)C=C1 RGHAZVBIOOEVQX-UHFFFAOYSA-N 0.000 claims 1
239000003085 diluting agent Substances 0.000 claims 1
238000001704 evaporation Methods 0.000 claims 1
230000008020 evaporation Effects 0.000 claims 1
229960002003 hydrochlorothiazide Drugs 0.000 claims 1
229960000939 metoprolol succinate Drugs 0.000 claims 1
229960001300 metoprolol tartrate Drugs 0.000 claims 1
WUBVEMGCQRSBBT-UHFFFAOYSA-N tert-butyl 4-(trifluoromethylsulfonyloxy)-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(OS(=O)(=O)C(F)(F)F)=CC1 WUBVEMGCQRSBBT-UHFFFAOYSA-N 0.000 claims 1
239000012071 phase Substances 0.000 description 6
150000002118 epoxides Chemical class 0.000 description 5
UEOWFGJMGUIGHC-UHFFFAOYSA-N 2-[[4-(2-methoxyethyl)phenoxy]methyl]oxirane Chemical compound C1=CC(CCOC)=CC=C1OCC1OC1 UEOWFGJMGUIGHC-UHFFFAOYSA-N 0.000 description 4
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
BSILSXIRKVLUHB-UHFFFAOYSA-N 4-(2-methoxyethyl)-5-propoxy-7-oxabicyclo[4.1.0]hepta-1(6),2,4-triene Chemical compound C1=C(CCOC)C(OCCC)=C2OC2=C1 BSILSXIRKVLUHB-UHFFFAOYSA-N 0.000 description 2
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 2
230000015572 biosynthetic process Effects 0.000 description 2
150000001875 compounds Chemical class 0.000 description 2
239000012141 concentrate Substances 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
239000000047 product Substances 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
238000005576 amination reaction Methods 0.000 description 1
230000007613 environmental effect Effects 0.000 description 1
239000012467 final product Substances 0.000 description 1
238000004817 gas chromatography Methods 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
238000002955 isolation Methods 0.000 description 1
239000010410 layer Substances 0.000 description 1
239000000203 mixture Substances 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
239000000376 reactant Substances 0.000 description 1
238000010992 reflux Methods 0.000 description 1
238000000926 separation method Methods 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
238000004448 titration Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/04—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reaction of ammonia or amines with olefin oxides or halohydrins
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/10—Antioedematous agents; Diuretics

NO19992401A 1996-11-20 1999-05-19 Ny fremgangsmåte for fremstilling av metoprolol NO311352B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
SE9604253A SE9604253D0 (sv)	1996-11-20	1996-11-20	New manufacturing process metoprolol
PCT/SE1997/001926 WO1998022426A1 (en)	1996-11-20	1997-11-18	New manufacturing process of metoprolol

Publications (3)

Publication Number	Publication Date
NO992401D0 NO992401D0 (no)	1999-05-19
NO992401L NO992401L (no)	1999-07-13
NO311352B1 true NO311352B1 (no)	2001-11-19

Family

ID=20404680

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19992401A NO311352B1 (no)	1996-11-20	1999-05-19	Ny fremgangsmåte for fremstilling av metoprolol

Country Status (36)

Country	Link
US (1)	US6252113B1 (pt)
EP (1)	EP0942899B1 (pt)
JP (1)	JP4039640B2 (pt)
KR (1)	KR100544560B1 (pt)
CN (1)	CN1128786C (pt)
AR (1)	AR010069A1 (pt)
AT (1)	ATE234273T1 (pt)
AU (1)	AU728270B2 (pt)
BR (1)	BR9713370A (pt)
CA (1)	CA2269941A1 (pt)
CZ (1)	CZ174499A3 (pt)
DE (1)	DE69719788T2 (pt)
DK (1)	DK0942899T3 (pt)
EE (1)	EE03761B1 (pt)
EG (1)	EG21158A (pt)
ES (1)	ES2193365T3 (pt)
HK (1)	HK1022684A1 (pt)
HU (1)	HUP0002445A3 (pt)
ID (1)	ID21505A (pt)
IL (1)	IL129747A (pt)
IN (1)	IN187175B (pt)
IS (1)	IS1964B (pt)
MY (1)	MY119303A (pt)
NO (1)	NO311352B1 (pt)
NZ (1)	NZ335213A (pt)
PL (1)	PL191392B1 (pt)
PT (1)	PT942899E (pt)
RU (1)	RU2210565C2 (pt)
SA (1)	SA97180599B1 (pt)
SE (1)	SE9604253D0 (pt)
SK (1)	SK281990B6 (pt)
TR (1)	TR199901115T2 (pt)
TW (1)	TW412513B (pt)
UA (1)	UA66769C2 (pt)
WO (1)	WO1998022426A1 (pt)
ZA (1)	ZA9710005B (pt)

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US20050107635A1 (en) *	2003-11-14	2005-05-19	Mehra Janakraj K.	Metoprolol manufacturing process
WO2007141593A2 (en) *	2005-12-23	2007-12-13	Medichem, S.A.	Process for the preparation of metoprolol and its salts
US20080107726A1 (en) *	2006-11-01	2008-05-08	Pramod Kharwade	Compositions comprising beta-adrenergic receptor antagonists and diuretics
CN101607918B (zh) *	2008-06-16	2014-02-19	北京德众万全药物技术开发有限公司	一种美托洛尔的制备方法
WO2011056929A1 (en) *	2009-11-04	2011-05-12	Massachusetts Institute Of Technology	Continuous flow synthesis of amino alcohols using microreactors
US8680303B2 (en)	2010-03-01	2014-03-25	Massachusetts Institute Of Technology	Epoxidation catalysts
CN102381995B (zh) *	2010-08-31	2015-04-15	扬子江药业集团北京海燕药业有限公司	美托洛尔的制备方法
CN102432476A (zh) *	2010-09-29	2012-05-02	湖南康普医药研究院	一种规模化制备琥珀酸美托洛尔的方法
CN102503843B (zh) *	2011-10-28	2013-10-23	山东阿如拉药物研究开发有限公司	一种美托洛尔盐的制备方法
KR101379383B1 (ko) *	2012-03-23	2014-04-02	주식회사 알에스텍	고순도 ⒮―메토프롤롤의 제조방법
CN103980134B (zh) *	2014-05-30	2015-09-30	安徽省新星药物开发有限责任公司	一种琥珀酸s-美托洛尔的制备方法
CN105820057B (zh) *	2016-04-22	2017-09-29	上海应用技术学院	一种制备美多心安的方法
CN106543015A (zh) *	2016-11-07	2017-03-29	上海应用技术大学	一种美多心安的制备方法
CN108299279B (zh) *	2018-02-09	2021-03-23	北京梅尔森医药技术开发有限公司	取代芳基胺醇化合物及其制备方法和用途
EP3768378A4 (en)	2018-03-22	2021-11-17	InCarda Therapeutics, Inc.	INNOVATIVE METHOD OF SLOWING THE VENTRICULAR RATE
CN111018724B (zh) *	2019-12-27	2022-11-08	江西美晶科技有限公司	一种美托洛尔及其制备方法
CN112645827A (zh) *	2020-12-25	2021-04-13	浙江普洛家园药业有限公司	一种连续合成美多心安及其盐的方法

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ES2011584A6 (es) *	1989-05-26	1990-01-16	Esteve Quimica Sa	Procedimiento industrial para la obtencion de una ariloxipropanolamina.
WO1992016197A1 (en)	1991-03-18	1992-10-01	Sepracor Inc.	Composition and method containing optically pure (s) metoprolol

1996
- 1996-11-18 NZ NZ335213A patent/NZ335213A/en unknown
- 1996-11-20 SE SE9604253A patent/SE9604253D0/xx unknown
- 1996-11-20 US US08/973,144 patent/US6252113B1/en not_active Expired - Lifetime
1997
- 1997-10-23 TW TW086115698A patent/TW412513B/zh active
- 1997-11-06 ZA ZA9710005A patent/ZA9710005B/xx unknown
- 1997-11-12 SA SA97180599A patent/SA97180599B1/ar unknown
- 1997-11-13 IN IN3275DE1997 patent/IN187175B/en unknown
- 1997-11-18 TR TR1999/01115T patent/TR199901115T2/xx unknown
- 1997-11-18 RU RU99109477/04A patent/RU2210565C2/ru not_active IP Right Cessation
- 1997-11-18 PT PT97913641T patent/PT942899E/pt unknown
- 1997-11-18 AT AT97913641T patent/ATE234273T1/de not_active IP Right Cessation
- 1997-11-18 PL PL333541A patent/PL191392B1/pl not_active IP Right Cessation
- 1997-11-18 AU AU50776/98A patent/AU728270B2/en not_active Ceased
- 1997-11-18 UA UA99042412A patent/UA66769C2/uk unknown
- 1997-11-18 JP JP51107298A patent/JP4039640B2/ja not_active Expired - Fee Related
- 1997-11-18 HU HU0002445A patent/HUP0002445A3/hu unknown
- 1997-11-18 EG EG122697A patent/EG21158A/xx active
- 1997-11-18 DE DE69719788T patent/DE69719788T2/de not_active Expired - Fee Related
- 1997-11-18 CN CN97199796A patent/CN1128786C/zh not_active Expired - Lifetime
- 1997-11-18 WO PCT/SE1997/001926 patent/WO1998022426A1/en not_active Application Discontinuation
- 1997-11-18 ES ES97913641T patent/ES2193365T3/es not_active Expired - Lifetime
- 1997-11-18 ID IDW990343D patent/ID21505A/id unknown
- 1997-11-18 CA CA002269941A patent/CA2269941A1/en not_active Abandoned
- 1997-11-18 EE EEP199900202A patent/EE03761B1/xx not_active IP Right Cessation
- 1997-11-18 KR KR1019997004401A patent/KR100544560B1/ko not_active IP Right Cessation
- 1997-11-18 CZ CZ991744A patent/CZ174499A3/cs unknown
- 1997-11-18 SK SK564-99A patent/SK281990B6/sk unknown
- 1997-11-18 DK DK97913641T patent/DK0942899T3/da active
- 1997-11-18 EP EP97913641A patent/EP0942899B1/en not_active Expired - Lifetime
- 1997-11-18 BR BR9713370A patent/BR9713370A/pt not_active Application Discontinuation
- 1997-11-18 IL IL12974797A patent/IL129747A/xx not_active IP Right Cessation
- 1997-11-19 AR ARP970105420A patent/AR010069A1/es unknown
- 1997-11-19 MY MYPI97005544A patent/MY119303A/en unknown
1999
- 1999-04-26 IS IS5034A patent/IS1964B/is unknown
- 1999-05-19 NO NO19992401A patent/NO311352B1/no unknown
2000
- 2000-03-20 HK HK00101688A patent/HK1022684A1/xx not_active IP Right Cessation

Also Published As

Publication number	Publication date
DK0942899T3 (da)	2003-06-02
IL129747A (en)	2003-01-12
ES2193365T3 (es)	2003-11-01
JP4039640B2 (ja)	2008-01-30
SK281990B6 (sk)	2001-09-11
AR010069A1 (es)	2000-05-15
ZA9710005B (en)	1998-05-20
PL191392B1 (pl)	2006-05-31
PT942899E (pt)	2003-06-30
IS1964B (is)	2004-12-15
ATE234273T1 (de)	2003-03-15
IL129747A0 (en)	2000-02-29
EG21158A (en)	2000-12-31
NZ335213A (en)	2001-02-23
TW412513B (en)	2000-11-21
NO992401D0 (no)	1999-05-19
IS5034A (is)	1999-04-26
KR20000057134A (ko)	2000-09-15
CN1237958A (zh)	1999-12-08
EE9900202A (et)	1999-12-15
DE69719788D1 (de)	2003-04-17
SA97180599B1 (ar)	2006-03-25
EP0942899B1 (en)	2003-03-12
CN1128786C (zh)	2003-11-26
HUP0002445A3 (en)	2001-09-28
SE9604253D0 (sv)	1996-11-20
JP2001503388A (ja)	2001-03-13
NO992401L (no)	1999-07-13
DE69719788T2 (de)	2004-02-12
AU728270B2 (en)	2001-01-04
EE03761B1 (et)	2002-06-17
BR9713370A (pt)	2000-03-21
HUP0002445A2 (hu)	2001-08-28
KR100544560B1 (ko)	2006-01-24
RU2210565C2 (ru)	2003-08-20
IN187175B (pt)	2002-02-23
CA2269941A1 (en)	1998-05-28
WO1998022426A1 (en)	1998-05-28
AU5077698A (en)	1998-06-10
SK56499A3 (en)	2000-03-13
HK1022684A1 (en)	2000-08-18
EP0942899A1 (en)	1999-09-22
MY119303A (en)	2005-04-30
CZ174499A3 (cs)	1999-11-17
TR199901115T2 (xx)	1999-07-21
US6252113B1 (en)	2001-06-26
UA66769C2 (uk)	2004-06-15
ID21505A (id)	1999-06-17

Publication	Publication Date	Title
NO311352B1 (no)	2001-11-19	Ny fremgangsmåte for fremstilling av metoprolol
US20070167624A1 (en)	2007-07-19	Process for preparing 1-methoxymethyl 5,5-diphenybarbituric acid
NO165496B (no)	1990-11-12	Analogifremgangsmaate for fremstilling av nye epoksysteroider.
Neale et al.	1965	The influence of solvent and chloramine structure on the free-radical rearrangement products of N-chlorodialkylamines
KR100244880B1 (ko)	2000-03-02	2-클로로-5-알킬아미노메틸-피리딘의제조방법
US6150528A (en)	2000-11-21	Method for producing 5-aminomethyl-2-chloropyridines
EP0169602B1 (en)	1989-03-01	Preparation of n-substituted azetidine 3-carboxylic acid derivatives
US4289907A (en)	1981-09-15	Process for preparing N-alkyl-nitroanilines
CA1182819A (en)	1985-02-19	Process producing 2,4-diamin-(3,5-dimethoxy-4- methoxy-ethoxy-benzyl)-pyrimidine
MXPA99004570A (en)	2000-02-02	New manufacturing process of metoprolol
US4395572A (en)	1983-07-26	Process for preparing N-alkyl-nitroanilines
US5973169A (en)	1999-10-26	Ipriflavone preparation process
US20080119662A1 (en)	2008-05-22	One Spot Synthesis of Citalopram from 5-Cyanophthalide
US6307103B1 (en)	2001-10-23	Process for the preparation of 1,1,1-trifluoro-2-aminoalkanes
NO885185L (no)	1989-05-29	Fremgangsmaate til fremstilling av alkanolaminderivater.
IE47805B1 (en)	1984-06-27	2,3-dihydro-4h-1-benzopyran-4-one o-carbamoyl oximes
US7501515B2 (en)	2009-03-10	Polymorphic form of 17-β-(N-ter. butyl carbamoyl)-4-aza-5-α-androst-1-en-3-one
EP1044960B1 (en)	2002-12-04	Process for the preparation of 1,1,1-trifluoro-2-aminoalkanes
EP0579096B1 (en)	1999-05-26	A process for the preparation of 5-(3-tert.-butylamino-2-hydroxypropoxy)-3,4-dihydro- carbostyryl.
RU2204556C2 (ru)	2003-05-20	Способ получения 1-(парахлорбензгидрил)-4-(2-оксиэтил)пиперазина
NO148450B (no)	1983-07-04	Fremgangsmaate ved fremstilling av 1-(2,6-dimethylfenoxy)-2-amino-propan.
NO813067L (no)	1982-03-11	Fremgangsmaate ved fremstilling av apovincaminsyreestere
JP2018503640A (ja)	2018-02-08	４−シアノピペリジン塩酸塩を調製する方法
NO316069B1 (no)	2003-12-08	Fremgangsmåte for fremstilling av 2-(2-brometyl)-naftalen
GB2153826A (en)	1985-08-29	Unsaturated carboxylic acid