HRP20030233A2 - Process for the preparation of substituted phenylacetonitriles - Google Patents
Process for the preparation of substituted phenylacetonitriles Download PDFInfo
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- HRP20030233A2 HRP20030233A2 HR20030233A HRP20030233A HRP20030233A2 HR P20030233 A2 HRP20030233 A2 HR P20030233A2 HR 20030233 A HR20030233 A HR 20030233A HR P20030233 A HRP20030233 A HR P20030233A HR P20030233 A2 HRP20030233 A2 HR P20030233A2
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- alkyl
- phase transfer
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- 238000000034 method Methods 0.000 title claims description 23
- 238000002360 preparation method Methods 0.000 title claims description 10
- 150000007962 benzene acetonitriles Chemical class 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims description 38
- 238000006243 chemical reaction Methods 0.000 claims description 22
- 239000003444 phase transfer catalyst Substances 0.000 claims description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 19
- 239000002585 base Substances 0.000 claims description 17
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 12
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 7
- 239000007864 aqueous solution Substances 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 4
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 claims description 3
- 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 claims description 2
- 229910001854 alkali hydroxide Inorganic materials 0.000 claims description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 150000003983 crown ethers Chemical group 0.000 claims description 2
- 150000004820 halides Chemical class 0.000 claims description 2
- 150000004714 phosphonium salts Chemical group 0.000 claims description 2
- 150000003242 quaternary ammonium salts Chemical group 0.000 claims description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical group [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 4
- PACGLQCRGWFBJH-UHFFFAOYSA-N 2-(4-methoxyphenyl)acetonitrile Chemical compound COC1=CC=C(CC#N)C=C1 PACGLQCRGWFBJH-UHFFFAOYSA-N 0.000 description 3
- SUSQOBVLVYHIEX-UHFFFAOYSA-N o-phenylene-diaceto-nitrile Natural products N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 229960004688 venlafaxine Drugs 0.000 description 2
- PNVNVHUZROJLTJ-UHFFFAOYSA-N venlafaxine Chemical group C1=CC(OC)=CC=C1C(CN(C)C)C1(O)CCCCC1 PNVNVHUZROJLTJ-UHFFFAOYSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Catalysts (AREA)
Description
Predloženi izum se odnosi na postupke za pripravu supstituiranih fenilacetonitrila, koji se provodi reakcijom alkoksifenilacetonitrila sa cikloheksanonom u prisutnosti vodene baze i katalizatora faznog prijenosa.
Poznato je da se supstituirani fenilacetonitrili formule (1) mogu upotrijebiti posebno kao intermedijati u sintezi za pripravu farmaceutski aktivnih tvari koje su antidepresanti središnjeg nervnog sistema. Važna tvar je Venlafaxine (vidi Merck Index 12. izdanje, 1996, br. 10079). Priprava tog spoja opisana je u US-A-4,535,186.
Prema US-A-4,535,186, primjer 1, intermedijati formule (1) se proizvode reakcijom p-metoksifenilacetonitrila i cikloheksanona u prisutnosti n-butil litija i organskog otapala, kao što su tetrahidrofuran i cikloheksan. Ukupno iskorištenje prema tom postupku je nisko i ne prelazi 50%. Osim toga, upotreba n-butil litija i organskih otapala uzrokuje kako ekološke tako također i gospodarske nedostatke i ima za posljedicu postupak u kojem se uvjeti reakcije moraju pažljivo kontrolirati.
Cilj predloženog izuma je osigurati postupak za pripravu supstituiranih fenilacetonitrila s poboljšanim iskorištenjem koji također ispunjava kako ekološke tako također i gospodarske zahtjeve i u kojem se uvjeti reakcije mogu lako kontrolirati.
Predloženi izum odnosi se na postupak za pripravu spoja formule
[image]
u kojoj ri predstavlja nesupstituirani ili supstituirani alkil, koji uključuje reakciju spoja formule
[image]
sa spojem formule
[image]
u prisutnosti vodene baze i katalizatora faznog prijenosa.
Ponajprije, R1 je C1-C10-alkil, posebno C1-C4-alkil; jedan primjer supstituenta alkilnog radikala R1 je fenil. Primjeri za R1 su metil, etil, n- ili i-propil, n-, i-, sek- ili terc-butil, i benzil. Ponajbolje, R1 je metil.
Upotrijebljena količina spoja formule (3) je ponajprije 0,9 do 1,8, ponajprije pribl. 1 do 1,6 molarnog ekvivalenta prema molarnoj količini spoja formule (2).
Vodena baza je ponajprije vodena otopina alkalijskog hidroksida, posebno vodena otopina natrijevog hidroksida ili kalijevog hidroksid, ponajbolje natrijevog hidroksida.
Upotrijebljena količina baze je ponajprije 0,05 do 4, još bolje 0,1 do 2 i ponajbolje 0,25 do 1,5 molarnog ekvivalenta prema molarnoj količini spoja formule (2).
Vodena otopina baze obično sadrži 1 do 70%, ponajprije 1 do 60 mas. % baze, računato prema ukupnoj masi vode i baze. Minimalna količina baze je 3%, ponajprije 5 mas. %. Maksimalna količina baze je ponajprije 50%, ponajbolje 25%.
Primjeri katalizatora faznog prijenosa su opisani u WO-A-97/20810, strana 6, red 13 do strane 7, red 5, koji je ovdje uvršten kao literatura.
Prednosni katalizatori faznog prijenosa su kvaterne amonijeve soli, kvaterne fosfonijeve soli ili kruna eteri.
Najpovoljniji katalizator faznog prijenosa je spoj formule
N(R2)4+Hal- (4a) ili P(R3)4+Hal- (4b),
u kojoj radikali R2 i R3 međusobno neovisno predstavljaju fenil ili alkil koji nije supstituiran ili je supstituiran s fenilom, i Hal- je halogenid.
R2 i R3 predstavljaju ponajprije C1-C16-alkil, benzil ili fenil, naročito C1-C4-alkil, benzil ili fenil. Ponajbolje, R2 i R3 su C1-C4-alkil ili benzil, naročito C1-C4-alkil. Visoku prednost daje se radikalima R2 i R3 koji predstavljaju C3-C4-alkil, naročito butil.
Primjeri za Hal- jesu fluorid, klorid, bromid i jodid. Hal je ponajprije fluorid, klorid ili bromid, ponajbolje klorid ili bromid. Visoku prednost daje se bromidu.
Prednost se daje katalizatorima faznog prijenosa formule (4a). Katalizator faznog prijenosa kojem se daje visoku prednost je tetrabutilamonijev klorid ili bromid, naročito tetrabutilamonijev bromid.
Može se naravno također upotrijebiti u mješavinu katalizatora faznog prijenosa.
Upotrijebljena količina katalizatora faznog prijenosa je u pravilu u rasponu od 0,0001 do 0,1, naročito 0,0005 do 0,05 molarnih ekvivalenta prema molarnoj količini spoja formule (2). Prednost se daje minimalnoj količini katalizatora faznog prijenosa od 0,001.
Reakcija spoja formule (2) sa spojem formule (3) provodi se pri temperaturi od 0 do 60°C, naročito 0 do 40°C. Reakciju se provodi ponajprije pri temperaturi od 15 do 35°C, naročito pri sobnoj temperaturi.
Za reakciju nije potrebno dodavati nikakva organska otapala. To znači da se reakcija uobičajeno provodi dodatkom reaktanata, vodene otopine baze i katalizatora faznog prijenosa.
U skladu s prednosnom izvedbom, reakcija spoja formule (2) sa spojem formule (3) provodi se u prisutnosti vodene otopine natrijevog ili kalijevog hidroksida, posebno natrijevog hidroksida, i u prisutnosti katalizatora faznog prijenosa formule (4a) , u kojoj R2 predstavlja C1-C4-alkil, naročito butil, i Hal- je klorid ili bromid.
Po završetku reakcije željeni proizvod se može odvojiti, na primjer, filtracijom. Po želji, proizvod se može isprati i zatim osušiti.
Osim toga, predloženi izum se odnosi na postupak za pripravu spoja formule
[image]
u kojoj R1 predstavlja nesupstituirani ili supstituirani alkil, koji obuhvaća reakciju spoja formule
[image]
sa spojem formule
[image]
u prisutnosti vodene baze i katalizatora faznog prijenosa, čime se dobije spoj formule
[image]
u kojoj je R1 definiran kao gore, i pretvorbu spoja formule (1) u spoj formule (5).
Kako je gore spomenuto, spojevi formule (1) su prikladni intermedijati za pripravu Venlafaxina kojeg prikazuje formula (5).
Za R1 se primjenjuju iste definicije i prednosti kao gore. R1 je ponajbolje metil.
Pretvorba spoja formule (1) u spoj formule (5) može se provesti u skladu s poznatim postupcima. Takova pretvorba i uvjeti reakcije koji se mogu primijeniti opisani su u US-A-4,535,186 (vidi posebno primjere 2 i 3).
Općenito, postupak takove pretvorbe obuhvaća slijedeće stupnjeve:
[image]
Stupanj A) može se provesti katalitičkim hidrogeniranjem (na primjer rodij na glini).
Stupanj B) može se provesti reakcijom spoja formule (6) s formaldehidom, mravljom kiselinom u velikom suvišku vode.
U skladu s predloženim izumom, intermedijati formule (1) mogu se dobiti u visokim iskorištenjima. Također se može prištedjeti na upotrebi organskih otapala i također skupih baza. Osim toga reakciju se može lako kontrolirati.
Slijedeći primjeri prikazuju izum.
Primjeri 1 do 8
(4-metoksifenil)acetonitril i cikloheksanon se pomiješaju i griju/hlade na željenu temperaturu navedenu u slijedećoj tablici. Katalizator faznog prijenosa (PTC) i vodenu otopinu baze se dodaje uz snažno miješanje. Dobivenu reakcijsku smjesu se miješa tijekom vremena koje je navedeno u slijedećoj tablici, i zatim se profiltrira. Kruti proizvod se ispere s vodom i osuši u vakuumu.
Uvjeti reakcije su navedeni u slijedećoj tablici. Ekvivalenti navedeni u tablici su molarni ekvivalenti prema molarnoj količini (4-metoksifenil)acetonitrila.
Tablica: Eksperimentalni uvjeti
[image]
TBAB = tetrabutilamonijev bromid
TBACI = tetrabutilamonijev klorid
Claims (14)
1. Postupak za pripravu spoja formule
[image]
u kojoj R1 predstavlja nesupstituirani ili supstituirani alkil, naznačen time, da obuhvaća reakciju spoja formule
[image]
sa spojem formule
[image]
u prisutnosti vodene baze i katalizatora faznog prijenosa.
2. Postupak prema zahtjevu 1, naznačen time, da ri predstavlja C1-C4-alkil koji nije supstituiran ili je supstituiran s fenilom.
3. Postupak prema zahtjevu 1 ili 2, naznačen time, da ri predstavlja metil.
4. Postupak prema bilo kojem zahtjevu 1 do 3, naznačen time, da vodena baza je vodena otopina alkalijskog hidroksida.
5. Postupak prema bilo kojem zahtjevu 1 do 4, naznačen time, da vodena baza je vodena otopina natrijevog hidroksida ili kalijevog hidroksida, ponajprije natrijevog hidroksida.
6. Postupak prema bilo kojem zahtjevu 1 do 5, naznačen time, da katalizator faznog prijenosa je kvaterna amonijeva sol, kvaterna fosfonijeva sol ili kruna eter.
7. Postupak prema bilo kojem zahtjevu 1 do 6, naznačen time, da katalizator faznog prijenosa je spoj formule
N(R2)4+ Hal- (4a) ili P(R3)4+Hal- (4b) ,
u kojoj radikali R2 i R3 međusobno neovisno predstavljaju fenil ili alkil koji nije supstituiran ili je supstituiran s fenilom, i Hal- je halogenid.
8. Postupak prema zahtjevu 7, naznačen time, da R2 i R3 predstavljaju C1-C16-alkil, benzil ili fenil.
9. Postupak prema zahtjevu 7 ili 8, naznačen time, da katalizator faznog prijenosa je spoj formule (4a) i R2 je C1-C4-alkil, ponajprije butil.
10. Postupak prema bilo kojem zahtjevu 7 do 9, naznačen time, da Hal- je fluorid, klorid ili bromid, ponajprije klorid ili bromid.
11. Postupak prema bilo kojem zahtjevu 1 do 10, naznačen time, da se reakcija spoja formule (2) sa spojem formule (3) provodi pri temperaturi od 0 do 60°C.
12. Postupak prema bilo kojem zahtjevu 1 do 11, naznačen time, da se reakcija spoja formule (2) sa spojem formule (3) provodi u prisutnosti vodene otopine natrijevog ili kalijevog hidroksida i u prisutnosti katalizatora faznog prijenosa formule (4a) , u kojoj R2 predstavlja C1-C4-alkil, ponajprije butil, i Hal- je klorid ili bromid.
13. Postupak za pripravu spoja formule
[image]
u kojoj R1 predstavlja nesupstituirani ili supstituirani alkil, naznačen time, da obuhvaća reakciju spoja formule
[image]
sa spojem formule
[image]
u prisutnosti vodene baze i katalizatora faznog prijenosa,
[image]
čime se dobije spoj formule u kojoj je R1 definiran kao gore, i pretvorbu spoja formule (1) u spoj formule (5).
14. Postupak prema zahtjevu 13, naznačen time, da R1 je metil.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN705CH2000 | 2000-08-30 | ||
| PCT/EP2001/009665 WO2002018325A2 (en) | 2000-08-30 | 2001-08-21 | Process for the preparation of substituted phenylacetonitriles |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| HRP20030233A2 true HRP20030233A2 (en) | 2005-04-30 |
| HRPK20030233B3 HRPK20030233B3 (en) | 2006-07-31 |
Family
ID=34259929
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20030233A HRPK20030233B3 (en) | 2000-08-30 | 2003-03-28 | Process for the preparation of substituted phenylacetonitriles |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US6620960B2 (hr) |
| EP (1) | EP1313698B1 (hr) |
| JP (1) | JP4230220B2 (hr) |
| CN (1) | CN1276913C (hr) |
| AR (1) | AR030505A1 (hr) |
| AT (1) | ATE281429T1 (hr) |
| AU (2) | AU2001291785B2 (hr) |
| CA (1) | CA2418040C (hr) |
| DE (1) | DE60106946T2 (hr) |
| ES (1) | ES2231551T3 (hr) |
| HR (1) | HRPK20030233B3 (hr) |
| HU (1) | HU228031B1 (hr) |
| IL (2) | IL154220A0 (hr) |
| MX (1) | MXPA03001800A (hr) |
| PL (1) | PL201731B1 (hr) |
| PT (1) | PT1313698E (hr) |
| SK (1) | SK286860B6 (hr) |
| TR (1) | TR200300251T2 (hr) |
| TW (1) | TWI228118B (hr) |
| WO (1) | WO2002018325A2 (hr) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20030000217A (ko) * | 2001-06-22 | 2003-01-06 | 와이어쓰 | 시클로헥사놀 유도체의 제조방법 |
| KR100651353B1 (ko) * | 2002-02-01 | 2006-11-28 | 에스케이 주식회사 | 고수율로 벤라팩신 중간체를 연속적으로 제조하는 방법 |
| WO2003080565A1 (en) * | 2002-03-26 | 2003-10-02 | Global Bulk Drugs & Fine Chemicals Pvt. Ltd. | Process for the manufacture of substituted phenylacetonitriles |
| KR20060067613A (ko) * | 2004-12-15 | 2006-06-20 | 에스케이 주식회사 | 1-[시아노-(파라-메톡시페닐)메틸]시클로헥사놀의 제조방법 |
| CA2625832A1 (en) * | 2005-10-19 | 2007-04-26 | Vinod Kumar Kansal | Process for the preparation of highly pure 1-[2-dimethylamino-(4-methoxyphenyl) ethyl]cyclohexanol hydrochloride |
| WO2007094008A2 (en) * | 2006-02-16 | 2007-08-23 | Unichem Laboratories Limited | A novel process for preparation of venlafaxine hydrochloride and its intermediates |
| JP4763788B2 (ja) * | 2006-07-26 | 2011-08-31 | テバ ファーマシューティカル インダストリーズ リミティド | Ｏ−デスメチルベンラファキシンの合成方法 |
| WO2009070311A2 (en) | 2007-11-26 | 2009-06-04 | Teva Pharmaceutical Industries Ltd. | Crystal forms of o-desmethylvenlafaxine fumarate |
| WO2009084037A2 (en) * | 2007-12-20 | 2009-07-09 | Calyx Chemicals And Pharmaceuticals Ltd. | Novel process for preparation of o-desmethylvenlafaxine |
| CA2717580A1 (en) * | 2008-03-06 | 2009-12-17 | Teva Pharmaceutical Industries Ltd. | Processes for the preparation of o-desmethylvenlafaxine, free from its dimer impurities |
| US8569371B2 (en) | 2010-03-29 | 2013-10-29 | Pliva Hrvatska D.O.O. | Crystal forms of O-desmethylvenlafaxine fumarate |
| CN103342662B (zh) * | 2013-07-25 | 2015-01-14 | 南通瑞点化工科技有限公司 | 一种合成2-烷基苯乙腈的方法 |
| CN105777508B (zh) * | 2014-12-22 | 2019-01-25 | 上海泰禾国际贸易有限公司 | 一种1-(4-氯苯基)-2-环丙基-1-丙酮的合成方法 |
| EP3433231A4 (en) * | 2017-05-12 | 2019-12-18 | Agan Aroma&fine Chemicals Ltd. | PRODUCTION OF 2-CYCLOHEXYLIDEN-2-PHENYL-ACETONITRILE AND FRAGRANT STRUCTURAL ANALOGS THEREOF |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IE56324B1 (en) * | 1982-12-13 | 1991-06-19 | American Home Prod | Phenethylamine derivatives and intermediates therefor |
| GB8902209D0 (en) * | 1989-02-01 | 1989-03-22 | Wyeth John And Brother Limited | Preparation of cyclohexanol derivatives and novel thioamide intermediates |
| US6197828B1 (en) * | 1998-12-01 | 2001-03-06 | Sepracor, Inc. | Derivatives of (+)-venlafaxine and methods of preparing and using the same |
| US6504044B2 (en) * | 2001-02-28 | 2003-01-07 | Council Of Scientific And Industrial Research | Process for the preparation of 1-[cyano(aryl)methyl] cyclohexanol |
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2001
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- 2001-08-21 US US10/130,010 patent/US6620960B2/en not_active Expired - Fee Related
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- 2001-08-21 PL PL359712A patent/PL201731B1/pl not_active IP Right Cessation
- 2001-08-21 HU HU0300856A patent/HU228031B1/hu not_active IP Right Cessation
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- 2001-08-21 SK SK353-2003A patent/SK286860B6/sk not_active IP Right Cessation
- 2001-08-21 JP JP2002523443A patent/JP4230220B2/ja not_active Expired - Fee Related
- 2001-08-21 IL IL15422001A patent/IL154220A0/xx active IP Right Grant
- 2001-08-21 AT AT01971945T patent/ATE281429T1/de active
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| Publication number | Publication date |
|---|---|
| AR030505A1 (es) | 2003-08-20 |
| TWI228118B (en) | 2005-02-21 |
| EP1313698B1 (en) | 2004-11-03 |
| PL201731B1 (pl) | 2009-05-29 |
| HUP0300856A3 (en) | 2007-02-28 |
| PL359712A1 (en) | 2004-09-06 |
| PT1313698E (pt) | 2005-03-31 |
| AU9178501A (en) | 2002-03-13 |
| ATE281429T1 (de) | 2004-11-15 |
| HU228031B1 (en) | 2012-08-28 |
| CN1276913C (zh) | 2006-09-27 |
| JP2004507520A (ja) | 2004-03-11 |
| AU2001291785B2 (en) | 2005-12-15 |
| IL154220A (en) | 2008-06-05 |
| DE60106946D1 (de) | 2004-12-09 |
| US20030139623A1 (en) | 2003-07-24 |
| CA2418040A1 (en) | 2002-03-07 |
| TR200300251T2 (tr) | 2004-12-21 |
| HRPK20030233B3 (en) | 2006-07-31 |
| ES2231551T3 (es) | 2005-05-16 |
| JP4230220B2 (ja) | 2009-02-25 |
| WO2002018325A3 (en) | 2003-01-09 |
| US6620960B2 (en) | 2003-09-16 |
| IL154220A0 (en) | 2003-07-31 |
| HUP0300856A2 (hu) | 2003-09-29 |
| MXPA03001800A (es) | 2003-06-24 |
| DE60106946T2 (de) | 2005-11-03 |
| CN1608049A (zh) | 2005-04-20 |
| EP1313698A2 (en) | 2003-05-28 |
| SK286860B6 (sk) | 2009-06-05 |
| SK3532003A3 (en) | 2003-09-11 |
| WO2002018325A2 (en) | 2002-03-07 |
| CA2418040C (en) | 2010-07-06 |
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