JPS6239154B2 - - Google Patents
Info
- Publication number
- JPS6239154B2 JPS6239154B2 JP3822880A JP3822880A JPS6239154B2 JP S6239154 B2 JPS6239154 B2 JP S6239154B2 JP 3822880 A JP3822880 A JP 3822880A JP 3822880 A JP3822880 A JP 3822880A JP S6239154 B2 JPS6239154 B2 JP S6239154B2
- Authority
- JP
- Japan
- Prior art keywords
- reaction
- ifenprodil
- methanol
- added
- hydroxypropiophenone
- Prior art date
- 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
Links
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 66
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 30
- RARSHUDCJQSEFJ-UHFFFAOYSA-N p-Hydroxypropiophenone Chemical compound CCC(=O)C1=CC=C(O)C=C1 RARSHUDCJQSEFJ-UHFFFAOYSA-N 0.000 claims description 30
- 239000002904 solvent Substances 0.000 claims description 17
- 238000005893 bromination reaction Methods 0.000 claims description 15
- 239000011541 reaction mixture Substances 0.000 claims description 15
- 238000010438 heat treatment Methods 0.000 claims description 14
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 230000031709 bromination Effects 0.000 claims description 5
- 150000002170 ethers Chemical class 0.000 claims description 5
- 229910000042 hydrogen bromide Inorganic materials 0.000 claims description 5
- 239000011261 inert gas Substances 0.000 claims description 5
- 238000003825 pressing Methods 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 3
- 238000010531 catalytic reduction reaction Methods 0.000 claims description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N 1-propanol Substances CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims 2
- 230000005587 bubbling Effects 0.000 claims 1
- UYNVMODNBIQBMV-UHFFFAOYSA-N 4-[1-hydroxy-2-[4-(phenylmethyl)-1-piperidinyl]propyl]phenol Chemical compound C1CC(CC=2C=CC=CC=2)CCN1C(C)C(O)C1=CC=C(O)C=C1 UYNVMODNBIQBMV-UHFFFAOYSA-N 0.000 description 26
- 229960003998 ifenprodil Drugs 0.000 description 25
- 239000013078 crystal Substances 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 23
- 238000003756 stirring Methods 0.000 description 21
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 18
- 229910052794 bromium Inorganic materials 0.000 description 18
- 238000006722 reduction reaction Methods 0.000 description 17
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- 239000003054 catalyst Substances 0.000 description 12
- 238000006482 condensation reaction Methods 0.000 description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 11
- DBOLXXRVIFGDTI-UHFFFAOYSA-N 4-benzylpyridine Chemical compound C=1C=NC=CC=1CC1=CC=CC=C1 DBOLXXRVIFGDTI-UHFFFAOYSA-N 0.000 description 10
- 238000000034 method Methods 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- 230000000704 physical effect Effects 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- QGSKPWWTAMUBEO-UHFFFAOYSA-N 4-[2-(4-benzylpiperidin-1-yl)-1-hydroxypropyl]phenol;hydrobromide Chemical compound Br.C1CC(CC=2C=CC=CC=2)CCN1C(C)C(O)C1=CC=C(O)C=C1 QGSKPWWTAMUBEO-UHFFFAOYSA-N 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 7
- 229910003446 platinum oxide Inorganic materials 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 235000011114 ammonium hydroxide Nutrition 0.000 description 4
- 238000005574 benzylation reaction Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- QQFSREJMXIMHQJ-UHFFFAOYSA-N 2-bromo-1-(4-hydroxyphenyl)propan-1-one Chemical compound CC(Br)C(=O)C1=CC=C(O)C=C1 QQFSREJMXIMHQJ-UHFFFAOYSA-N 0.000 description 3
- 239000005909 Kieselgur Substances 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000000862 absorption spectrum Methods 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- YALYLPKSKBQFJP-UHFFFAOYSA-N chloroform;n-ethylethanamine Chemical compound ClC(Cl)Cl.CCNCC YALYLPKSKBQFJP-UHFFFAOYSA-N 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 238000011981 development test Methods 0.000 description 3
- 238000000921 elemental analysis Methods 0.000 description 3
- -1 ketone compound Chemical class 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 239000011259 mixed solution Substances 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- IKFGSOJYHVTNDV-UHFFFAOYSA-N 1-(4-phenylmethoxyphenyl)propan-1-one Chemical compound C1=CC(C(=O)CC)=CC=C1OCC1=CC=CC=C1 IKFGSOJYHVTNDV-UHFFFAOYSA-N 0.000 description 2
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 2
- NRSXDJVBULRMMH-UHFFFAOYSA-N 2-(4-benzylpyridin-1-ium-1-yl)-1-(4-hydroxyphenyl)propan-1-one;bromide Chemical compound [Br-].C=1C=C(CC=2C=CC=CC=2)C=C[N+]=1C(C)C(=O)C1=CC=C(O)C=C1 NRSXDJVBULRMMH-UHFFFAOYSA-N 0.000 description 2
- LSQLSCUJBXFBRB-UHFFFAOYSA-N 2-bromo-1-(4-phenylmethoxyphenyl)propan-1-one Chemical compound C1=CC(C(=O)C(Br)C)=CC=C1OCC1=CC=CC=C1 LSQLSCUJBXFBRB-UHFFFAOYSA-N 0.000 description 2
- WLVPRARCUSRDNI-UHFFFAOYSA-N 2-hydroxy-1-phenyl-1-propanone Chemical group CC(O)C(=O)C1=CC=CC=C1 WLVPRARCUSRDNI-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 238000009423 ventilation Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- DMPRDSPPYMZQBT-CEAXSRTFSA-N Ifenprodil tartrate Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.C1CC(CC=2C=CC=CC=2)CCN1C(C)C(O)C1=CC=C(O)C=C1.C1CC(CC=2C=CC=CC=2)CCN1C(C)C(O)C1=CC=C(O)C=C1 DMPRDSPPYMZQBT-CEAXSRTFSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- JGDFBJMWFLXCLJ-UHFFFAOYSA-N copper chromite Chemical compound [Cu]=O.[Cu]=O.O=[Cr]O[Cr]=O JGDFBJMWFLXCLJ-UHFFFAOYSA-N 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 150000004292 cyclic ethers Chemical class 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229960000204 ifenprodil tartrate Drugs 0.000 description 1
- RPNNPZHFJPXFQS-UHFFFAOYSA-N methane;rhodium Chemical compound C.[Rh] RPNNPZHFJPXFQS-UHFFFAOYSA-N 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- BASFCYQUMIYNBI-BKFZFHPZSA-N platinum-200 Chemical compound [200Pt] BASFCYQUMIYNBI-BKFZFHPZSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Landscapes
- Hydrogenated Pyridines (AREA)
- Pyridine Compounds (AREA)
Priority Applications (14)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3822880A JPS56135468A (en) | 1980-03-27 | 1980-03-27 | Preparation of 1- 4-hydroxyphenyl -2- 4-benzylpiperidino -1- propanol and addition salt thereof |
| PH24937A PH16735A (en) | 1979-12-07 | 1980-12-03 | A new process for the preparation of 1-(4-hydroxyphenyl)-2-(4-benzylpiperidino)-1-propanol and acid addition salts thereof |
| GB8038771A GB2067187B (en) | 1979-12-07 | 1980-12-03 | Process for the preparation of 1-(4-hydroxyphenyl)-2-(4-benzylpiperidino)-1-propanol and acid addition salts thereof |
| CA000366167A CA1141387A (en) | 1979-12-07 | 1980-12-04 | Process for the preparation of 1-(4-hydroxyphenyl)-2- (4-benzylpiperidino)-1-propanol and acid-addition salts thereof |
| US06/213,033 US4377691A (en) | 1979-12-07 | 1980-12-04 | Process for the preparation of 1-(4-hydroxyphenyl)-2-(4-benzylpiperidino)-1-propanol and acid-addition salts thereof |
| FR8025923A FR2471374A1 (fr) | 1979-12-07 | 1980-12-05 | Nouveau procede pour la preparation du 1-(4-hydroxyphenyl)-2-(4-benzylpiperidino)-propanol et de ses sels d'addition d'acides |
| AR283504A AR229157A1 (es) | 1979-12-07 | 1980-12-05 | Procedimiento para la preparacion de 1-(4-hidroxifenil)-2-(4-bencilpiperidino)-1-propanol |
| DE19803045916 DE3045916A1 (de) | 1979-12-07 | 1980-12-05 | Verfahren zur herstellung von 4-benzyl- (alpha) -(p-hydroxyphenyl)- (beta) -methyl-1-piperidinaethanol und seinen salzen mit saeuren |
| IT26487/80A IT1148744B (it) | 1979-12-07 | 1980-12-05 | Processo per la preparazione di 1-(4-idrossifenil)-2-(4-benzilpiperidino)-1-propanolo e relativi sali di addizione con acido |
| ES497527A ES8200342A1 (es) | 1979-12-07 | 1980-12-05 | Un procedimiento para la preparacion de 1-(4-hidroxifenil)- 2-(4-bencilpiperidino)-1-propanol |
| CH9032/80A CH648550A5 (de) | 1979-12-07 | 1980-12-08 | Verfahren zur herstellung von 4-benzyl-alpha-(p-hydroxyphenyl)-beta-methyl-1-piperidinaethanol und seinen salzen mit saeuren. |
| BR8008020A BR8008020A (pt) | 1979-12-07 | 1980-12-08 | Processo para a preparacao de 1-(4-hidroxifenil)-2-(4-benzilpiperidino)-1-propanol e seus sais de adicao de acido |
| AT0597580A AT374181B (de) | 1979-12-07 | 1980-12-09 | Verfahren zur herstellung von 4-benzyl-alpha-(p |
| HK71984A HK71984A (en) | 1979-12-07 | 1984-09-20 | Process for the preparation of 1-(4-hydroxyphenyl)-2-(4-benzylpiperidino)-1- propanol and acid-addition salts |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3822880A JPS56135468A (en) | 1980-03-27 | 1980-03-27 | Preparation of 1- 4-hydroxyphenyl -2- 4-benzylpiperidino -1- propanol and addition salt thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS56135468A JPS56135468A (en) | 1981-10-22 |
| JPS6239154B2 true JPS6239154B2 (enrdf_load_stackoverflow) | 1987-08-21 |
Family
ID=12519443
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3822880A Granted JPS56135468A (en) | 1979-12-07 | 1980-03-27 | Preparation of 1- 4-hydroxyphenyl -2- 4-benzylpiperidino -1- propanol and addition salt thereof |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS56135468A (enrdf_load_stackoverflow) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01123066U (enrdf_load_stackoverflow) * | 1988-02-05 | 1989-08-22 |
-
1980
- 1980-03-27 JP JP3822880A patent/JPS56135468A/ja active Granted
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01123066U (enrdf_load_stackoverflow) * | 1988-02-05 | 1989-08-22 |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS56135468A (en) | 1981-10-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JPH022870B2 (enrdf_load_stackoverflow) | ||
| EP0002308A1 (en) | Catalytic hydrogenation process for the manufacture of aromatic amines | |
| JPS6239154B2 (enrdf_load_stackoverflow) | ||
| JPS6239153B2 (enrdf_load_stackoverflow) | ||
| JPS6321662B2 (enrdf_load_stackoverflow) | ||
| JPS5925779B2 (ja) | 立体異性脂環ジアミンの異性化法 | |
| JPS64946B2 (enrdf_load_stackoverflow) | ||
| US4377691A (en) | Process for the preparation of 1-(4-hydroxyphenyl)-2-(4-benzylpiperidino)-1-propanol and acid-addition salts thereof | |
| JP2016511761A (ja) | ４−ピペリジン−４−イル−ベンゼン−１，３−ジオール及びその塩の合成方法、並びに新規化合物ｔｅｒｔ−ブチル４−（２，４−ジヒドロキシ−フェニル）−４−ヒドロキシ−ピペリジン−１−カルボキシレート | |
| KR840001706B1 (ko) | 2-(4-벤질피페리디노)-1-(4-히드록시페닐)-1-프로파놀의 제조방법 | |
| JPS597699B2 (ja) | インドリン類の製造方法 | |
| JP2004507524A (ja) | ３−アミノメチル−４−ｚ−メトキシイミノピロリジンの新規な製造方法 | |
| CN115677559A (zh) | 一种昂丹司琼中间体四氢咔唑酮的一步合成方法 | |
| JP4032825B2 (ja) | ３，４−ジヒドロキシベンゾニトリルを製造する方法 | |
| JP4028945B2 (ja) | ４−（ピリジン−２−イル）ベンズアルデヒドの製造方法、中間体化合物、該化合物の製造方法、およびヒドラジン誘導体の製造方法 | |
| CN118638011A (zh) | 一种氯霉素中间体的合成方法 | |
| TWI252848B (en) | Process for the preparation of 5-formylphthalide | |
| JPS5846515B2 (ja) | インド−ル誘導体の製造方法 | |
| JPS61148161A (ja) | １−〔１−（４−ヒドロキシフエニルカルボニル）エチル〕−４−ベンジルピリジニウム塩 | |
| JP2001199985A (ja) | 高純度フェノチアジン化合物とその製造方法、およびその中間体の製造方法、並びにその中間体の原料の水和物と新規結晶 | |
| JPS5869828A (ja) | ３−フエノキシベンジルアルコ−ル類の製造方法 | |
| JPS58177969A (ja) | ピペリジノアルカノ−ル及びその酸付加塩の製造法 | |
| JPS6034951B2 (ja) | １−（４−ヒドロキシフエニル）−２−（４−ベンジルピペリジノ）プロパン−１−オ−ルの製造方法 | |
| JPS5946274A (ja) | ２−アルキル−４−アミノ−５−アミノメチルピリミジンの製法 | |
| JPS58126847A (ja) | ３，３′−ジアミノベンゾフエノンの製造法 |