CA2176763C - Misoprostol - Google Patents

Misoprostol

Info

Publication number: CA2176763C
Authority: CA; Canada
Prior art keywords: group; compound; reaction; lithium; vinyl
Prior art date: 1996-05-17
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

CA002176763A

Other languages

English (en)

Other versions

CA2176763A1 (fr

Inventor

Yee Fung Lu

Raymond So

Dan To

Casimir Antczak

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.)

Torcan Chemical Ltd

Original Assignee

Torcan Chemical Ltd

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.)

1996-05-17

Filing date

1996-05-17

Publication date

1998-09-29

1996-05-17 Application filed by Torcan Chemical Ltd filed Critical Torcan Chemical Ltd

1996-05-17 Priority to CA002176763A priority Critical patent/CA2176763C/fr

1996-06-30 Publication of CA2176763A1 publication Critical patent/CA2176763A1/fr

1997-05-06 Priority to AT97303062T priority patent/ATE236907T1/de

1997-05-06 Priority to EP97303062A priority patent/EP0807634B1/fr

1997-05-06 Priority to DE69720587T priority patent/DE69720587D1/de

1998-09-29 Application granted granted Critical

1998-09-29 Publication of CA2176763C publication Critical patent/CA2176763C/fr

2016-05-17 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

OJLOPKGSLYJEMD-URPKTTJQSA-N methyl 7-[(1r,2r,3r)-3-hydroxy-2-[(1e)-4-hydroxy-4-methyloct-1-en-1-yl]-5-oxocyclopentyl]heptanoate Chemical compound CCCCC(C)(O)C\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(=O)OC OJLOPKGSLYJEMD-URPKTTJQSA-N 0.000 title claims abstract description 15
229960005249 misoprostol Drugs 0.000 title claims abstract description 15
-1 alkyl lithium compound Chemical class 0.000 claims abstract description 51
238000000034 method Methods 0.000 claims abstract description 36
238000006243 chemical reaction Methods 0.000 claims abstract description 35
229910052744 lithium Inorganic materials 0.000 claims abstract description 24
229920002554 vinyl polymer Polymers 0.000 claims abstract description 23
229910000080 stannane Inorganic materials 0.000 claims abstract description 17
BZKFMUIJRXWWQK-UHFFFAOYSA-N Cyclopentenone Chemical class O=C1CCC=C1 BZKFMUIJRXWWQK-UHFFFAOYSA-N 0.000 claims abstract description 14
150000004820 halides Chemical class 0.000 claims abstract description 11
150000001875 compounds Chemical class 0.000 claims abstract description 10
125000002524 organometallic group Chemical group 0.000 claims abstract description 9
DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical group C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 claims description 18
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 14
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 12
229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 10
LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical group I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims description 10
239000011541 reaction mixture Substances 0.000 claims description 8
239000003446 ligand Substances 0.000 claims description 7
150000003180 prostaglandins Chemical class 0.000 claims description 7
229910021589 Copper(I) bromide Inorganic materials 0.000 claims description 5
125000000217 alkyl group Chemical group 0.000 claims description 5
230000000694 effects Effects 0.000 claims description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
239000001257 hydrogen Substances 0.000 claims description 4
229910052739 hydrogen Inorganic materials 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 3
CVUYUBZMSCEMFT-UHFFFAOYSA-N methyl 7-(5-oxo-3-triethylsilyloxycyclopenten-1-yl)heptanoate Chemical compound CC[Si](CC)(CC)OC1CC(=O)C(CCCCCCC(=O)OC)=C1 CVUYUBZMSCEMFT-UHFFFAOYSA-N 0.000 claims description 3
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
239000000376 reactant Substances 0.000 claims description 3
125000001931 aliphatic group Chemical group 0.000 claims description 2
125000003545 alkoxy group Chemical group 0.000 claims description 2
NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 claims description 2
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
229920006395 saturated elastomer Polymers 0.000 claims description 2
QPDPSYPQQVBCLH-UHFFFAOYSA-N trimethyl-[(e)-4-methyl-1-tributylstannyloct-1-en-4-yl]oxysilane Chemical compound CCCCC(C)(O[Si](C)(C)C)C\C=C\[Sn](CCCC)(CCCC)CCCC QPDPSYPQQVBCLH-UHFFFAOYSA-N 0.000 claims description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical group O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 claims 1
150000002431 hydrogen Chemical group 0.000 claims 1
230000015572 biosynthetic process Effects 0.000 abstract description 9
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
239000000203 mixture Substances 0.000 description 9
238000002360 preparation method Methods 0.000 description 9
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
239000007858 starting material Substances 0.000 description 6
238000003786 synthesis reaction Methods 0.000 description 6
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 5
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
239000000243 solution Substances 0.000 description 5
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 4
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 4
239000000047 product Substances 0.000 description 4
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
239000005749 Copper compound Substances 0.000 description 3
XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 3
239000000126 substance Substances 0.000 description 3
231100000331 toxic Toxicity 0.000 description 3
230000002588 toxic effect Effects 0.000 description 3
UWNADWZGEHDQAB-UHFFFAOYSA-N 2,5-dimethylhexane Chemical group CC(C)CCC(C)C UWNADWZGEHDQAB-UHFFFAOYSA-N 0.000 description 2
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
101100272976 Panax ginseng CYP716A53v2 gene Proteins 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
239000012267 brine Substances 0.000 description 2
239000006227 byproduct Substances 0.000 description 2
239000007795 chemical reaction product Substances 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
239000010949 copper Substances 0.000 description 2
238000010511 deprotection reaction Methods 0.000 description 2
230000008034 disappearance Effects 0.000 description 2
238000000605 extraction Methods 0.000 description 2
238000001914 filtration Methods 0.000 description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 2
239000010410 layer Substances 0.000 description 2
150000002642 lithium compounds Chemical class 0.000 description 2
229910052943 magnesium sulfate Inorganic materials 0.000 description 2
235000019341 magnesium sulphate Nutrition 0.000 description 2
239000012299 nitrogen atmosphere Substances 0.000 description 2
239000012044 organic layer Substances 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
238000000746 purification Methods 0.000 description 2
ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 2
238000007086 side reaction Methods 0.000 description 2
239000000741 silica gel Substances 0.000 description 2
229910002027 silica gel Inorganic materials 0.000 description 2
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
238000003756 stirring Methods 0.000 description 2
125000001424 substituent group Chemical group 0.000 description 2
WMSCYGTVHFMKNS-UHFFFAOYSA-N tributyl(methyl)stannane Chemical compound CCCC[Sn](C)(CCCC)CCCC WMSCYGTVHFMKNS-UHFFFAOYSA-N 0.000 description 2
OOAHNJDZICJECC-BHWPLRMJSA-N (z)-7-[(1r,2r,3r)-2-[(e,3r)-3-hydroxy-4,4-dimethyloct-1-enyl]-3-methyl-5-oxocyclopentyl]hept-5-enoic acid Chemical compound CCCCC(C)(C)[C@H](O)\C=C\[C@H]1[C@H](C)CC(=O)[C@@H]1C\C=C/CCCC(O)=O OOAHNJDZICJECC-BHWPLRMJSA-N 0.000 description 1
238000011925 1,2-addition Methods 0.000 description 1
XSGQFHNPNWBVPT-VFXMVCAWSA-N 15-methyl-15R-PGE2 Chemical compound CCCCC[C@@](C)(O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XSGQFHNPNWBVPT-VFXMVCAWSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
229910021593 Copper(I) fluoride Inorganic materials 0.000 description 1
JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 description 1
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
VKEQBMCRQDSRET-UHFFFAOYSA-N Methylone Chemical compound CNC(C)C(=O)C1=CC=C2OCOC2=C1 VKEQBMCRQDSRET-UHFFFAOYSA-N 0.000 description 1
239000002253 acid Substances 0.000 description 1
238000007259 addition reaction Methods 0.000 description 1
125000003342 alkenyl group Chemical group 0.000 description 1
235000019270 ammonium chloride Nutrition 0.000 description 1
229950002312 arbaprostil Drugs 0.000 description 1
150000001649 bromium compounds Chemical class 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
125000003636 chemical group Chemical group 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
229910052802 copper Inorganic materials 0.000 description 1
150000004699 copper complex Chemical class 0.000 description 1
150000001880 copper compounds Chemical class 0.000 description 1
229910001431 copper ion Inorganic materials 0.000 description 1
ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 1
BMRUOURRLCCWHB-UHFFFAOYSA-M copper(i) fluoride Chemical compound [Cu]F BMRUOURRLCCWHB-UHFFFAOYSA-M 0.000 description 1
RYGMFSIKBFXOCR-AHCXROLUSA-N copper-60 Chemical compound [60Cu] RYGMFSIKBFXOCR-AHCXROLUSA-N 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
VWWMOACCGFHMEV-UHFFFAOYSA-N dicarbide(2-) Chemical compound [C-]#[C-] VWWMOACCGFHMEV-UHFFFAOYSA-N 0.000 description 1
229950007459 enisoprost Drugs 0.000 description 1
229960003559 enprostil Drugs 0.000 description 1
KLKFAASOGCDTDT-UHFFFAOYSA-N ethoxymethoxyethane Chemical compound CCOCOCC KLKFAASOGCDTDT-UHFFFAOYSA-N 0.000 description 1
230000027119 gastric acid secretion Effects 0.000 description 1
KYBOHGVERHWSSV-VNIVIJDLSA-N gemeprost Chemical compound CCCCC(C)(C)[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCC\C=C\C(=O)OC KYBOHGVERHWSSV-VNIVIJDLSA-N 0.000 description 1
229960003480 gemeprost Drugs 0.000 description 1
231100001261 hazardous Toxicity 0.000 description 1
MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
150000004694 iodide salts Chemical class 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000011630 iodine Substances 0.000 description 1
GHXZPUGJZVBLGC-UHFFFAOYSA-N iodoethene Chemical class IC=C GHXZPUGJZVBLGC-UHFFFAOYSA-N 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
TWCQWABAGCMHLL-ROVQGQOSSA-N methyl (z)-7-[(1r,2r,3r)-2-[(e)-4-ethenyl-4-hydroxyoct-1-enyl]-3-hydroxy-5-oxocyclopentyl]hept-5-enoate Chemical compound CCCCC(O)(C=C)C\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(=O)OC TWCQWABAGCMHLL-ROVQGQOSSA-N 0.000 description 1
CIBHDGPIOICRGX-ZQCHCGQNSA-N methyl (z)-7-[(1r,2r,3r)-3-hydroxy-2-[(e)-4-hydroxy-4-methyloct-1-enyl]-5-oxocyclopentyl]hept-4-enoate Chemical compound CCCCC(C)(O)C\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CC\C=C/CCC(=O)OC CIBHDGPIOICRGX-ZQCHCGQNSA-N 0.000 description 1
PTOJVMZPWPAXER-VFJVYMGBSA-N methyl 7-[(1r,2r,3r)-3-hydroxy-2-[(e,3r)-3-hydroxy-4-phenoxybut-1-enyl]-5-oxocyclopentyl]hepta-4,5-dienoate Chemical compound O[C@@H]1CC(=O)[C@H](CC=C=CCCC(=O)OC)[C@H]1\C=C\[C@@H](O)COC1=CC=CC=C1 PTOJVMZPWPAXER-VFJVYMGBSA-N 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
150000002902 organometallic compounds Chemical class 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
WGJJROVFWIXTPA-OALUTQOASA-N prostanoic acid Chemical class CCCCCCCC[C@H]1CCC[C@@H]1CCCCCCC(O)=O WGJJROVFWIXTPA-OALUTQOASA-N 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
SPOAFZKFCYREMW-FWYLUGOYSA-N rioprostil Chemical compound CCCCC(C)(O)C\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCCO SPOAFZKFCYREMW-FWYLUGOYSA-N 0.000 description 1
229950004712 rioprostil Drugs 0.000 description 1
239000002904 solvent Substances 0.000 description 1
KXCAEQNNTZANTK-UHFFFAOYSA-N stannane Chemical compound [SnH4] KXCAEQNNTZANTK-UHFFFAOYSA-N 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
229950008298 trimoprostil Drugs 0.000 description 1
229950011361 viprostol Drugs 0.000 description 1
239000002699 waste material Substances 0.000 description 1
239000003643 water by type Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C405/00—Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins ; Analogues or derivatives thereof
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/22—Tin compounds

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)

CA002176763A 1996-05-17 1996-05-17 Misoprostol Expired - Fee Related CA2176763C (fr)

Priority Applications (4)

Application Number	Priority Date	Filing Date	Title
CA002176763A CA2176763C (fr)	1996-05-17	1996-05-17	Misoprostol
AT97303062T ATE236907T1 (de)	1996-05-17	1997-05-06	Misoprostol, verfahren zur deren herstellung mit verwendung eines organometall-kupferkomplexes
EP97303062A EP0807634B1 (fr)	1996-05-17	1997-05-06	Misoprostol, procédé pour le préparer utilisant un complexe cuivreux organométallique
DE69720587T DE69720587D1 (de)	1996-05-17	1997-05-06	Misoprostol, Verfahren zur deren Herstellung mit Verwendung eines Organometall-Kupferkomplexes

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
CA002176763A CA2176763C (fr)	1996-05-17	1996-05-17	Misoprostol

Publications (2)

Publication Number	Publication Date
CA2176763A1 CA2176763A1 (fr)	1996-06-30
CA2176763C true CA2176763C (fr)	1998-09-29

Family

ID=4158212

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002176763A Expired - Fee Related CA2176763C (fr)	1996-05-17	1996-05-17	Misoprostol

Country Status (1)

Country	Link
CA (1)	CA2176763C (fr)

1996
- 1996-05-17 CA CA002176763A patent/CA2176763C/fr not_active Expired - Fee Related

Also Published As

Publication number	Publication date
CA2176763A1 (fr)	1996-06-30

Legal Events

Date	Code	Title	Description
1996-05-17	EEER	Examination request
2011-05-17	MKLA	Lapsed

Publication	Publication Date	Title
Ostwald et al.	1994	Catalytic Asymmetric Addition of Polyfunctional Dialkylzincs to. beta.-Stannylated and. beta.-Silylated Unsaturated Aldehydes
EP1385819B1 (fr)	2015-12-23	Procede de preparation de derives de prostaglandine et produit de depart stereospecifique correspondant
CA1173826A (fr)	1984-09-04	Acides 15-desoxy-16-hydroxy-prostanoiques substitues en 16 et congeneres
Corriu et al.	1991	Pentacoordinate dihydridosilicates: synthesis, structure, and aspects of their reactivity
Becker et al.	1989	Hypervalent silicon hydrides: evidence for their intermediacy in the exchange reactions of di-and tri-hydrogenosilanes catalysed by hydrides (NaH, KH and LiAlH4)
JPH07116075B2 (ja)	1995-12-13	不飽和アルコール化合物の製造方法
US5684177A (en)	1997-11-04	Misoprostol
US3932479A (en)	1976-01-13	Lithium 3-triphenylmethoxy-1-trans-alkenyl-dialkyl alanates
CA2176763C (fr)	1998-09-29	Misoprostol
US4060540A (en)	1977-11-29	Novel 3-triphenylmethoxy-1-alkynes, 3-triphenyl-methoxy-1-trans-alkenyl-dialkyl-alanes, and lithium 3-triphenylmethoxy-1-trans-alkenyl-dialkyl alanates
US4578505A (en)	1986-03-25	Allenic prostanoic acid derivatives
EP0807634B1 (fr)	2003-04-09	Misoprostol, procédé pour le préparer utilisant un complexe cuivreux organométallique
EP0115844A1 (fr)	1984-08-15	3-Oxaprostaglandines
JP2528972B2 (ja)	1996-08-28	アルキニル化合物の連続製造方法
CA1201118A (fr)	1986-02-25	Addition conjuguee d'organocuprates obtenus a partir de cyanure de cuivre (i) et de vinylstannanes, utiles pour la synthese d'analogues de la prostglandine
EP0294757A2 (fr)	1988-12-14	Procédé pour la préparation de complexes de cuprate d'ordre supérieur
US3943157A (en)	1976-03-09	Synthesis of codling moth attractant
JP4163763B2 (ja)	2008-10-08	シクロペンタジエン系化合物のアルキル化方法
Bellina et al.	1994	Synthesis of 2-tributylstannyl-1-alkenes from 2-tributylstannyl-2-propen-1-yl acetate
US5405981A (en)	1995-04-11	Copper catalyzed coupling reactions
KR100208496B1 (ko)	1999-07-15	유기지르코늄 화합물을 사용하여 프로스타글란딘 유사체를 제조하는 방법
EP0943607B1 (fr)	2005-01-26	Procede de preparation de prostaglandines
CZ278597A3 (cs)	1998-01-14	Způsob přípravy prostaglandinu E1, E2 a analog za použití furyl-měďnatých sloučenin
US4123456A (en)	1978-10-31	Novel 11-hydroxy-9-keto-5,6-cis-13,14-cis-prostadienoic acid derivatives
US4343949A (en)	1982-08-10	Novel 2-substituted-3,4-epoxycyclopentan-1-ones, 2-substituted-3,4-epoxycyclopentan-1-ols, and various 2-substituted-cyclopentenones