FR2471374A1 - Nouveau procede pour la preparation du 1-(4-hydroxyphenyl)-2-(4-benzylpiperidino)-propanol et de ses sels d'addition d'acides - Google Patents
Nouveau procede pour la preparation du 1-(4-hydroxyphenyl)-2-(4-benzylpiperidino)-propanol et de ses sels d'addition d'acides Download PDFInfo
- Publication number
- FR2471374A1 FR2471374A1 FR8025923A FR8025923A FR2471374A1 FR 2471374 A1 FR2471374 A1 FR 2471374A1 FR 8025923 A FR8025923 A FR 8025923A FR 8025923 A FR8025923 A FR 8025923A FR 2471374 A1 FR2471374 A1 FR 2471374A1
- Authority
- FR
- France
- Prior art keywords
- mixture
- reaction
- added
- ifenprodil
- crystals
- 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.)
- Granted
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- 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 title claims abstract description 78
- 238000000034 method Methods 0.000 title claims abstract description 34
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- 150000003839 salts Chemical class 0.000 title claims abstract description 10
- 239000002253 acid Substances 0.000 title claims abstract description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 225
- 239000000203 mixture Substances 0.000 claims abstract description 148
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 82
- 229960003998 ifenprodil Drugs 0.000 claims abstract description 75
- 239000011541 reaction mixture Substances 0.000 claims abstract description 66
- RARSHUDCJQSEFJ-UHFFFAOYSA-N p-Hydroxypropiophenone Chemical compound CCC(=O)C1=CC=C(O)C=C1 RARSHUDCJQSEFJ-UHFFFAOYSA-N 0.000 claims abstract description 41
- 239000002904 solvent Substances 0.000 claims abstract description 39
- 238000010992 reflux Methods 0.000 claims abstract description 13
- -1 HYDROGEN FORM Chemical group 0.000 claims abstract description 11
- ABGXADJDTPFFSZ-UHFFFAOYSA-N 4-benzylpiperidine Chemical compound C=1C=CC=CC=1CC1CCNCC1 ABGXADJDTPFFSZ-UHFFFAOYSA-N 0.000 claims abstract description 3
- 239000012046 mixed solvent Substances 0.000 claims abstract description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 56
- 238000006243 chemical reaction Methods 0.000 claims description 56
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 53
- DBOLXXRVIFGDTI-UHFFFAOYSA-N 4-benzylpyridine Chemical compound C=1C=NC=CC=1CC1=CC=CC=C1 DBOLXXRVIFGDTI-UHFFFAOYSA-N 0.000 claims description 49
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 42
- 238000005893 bromination reaction Methods 0.000 claims description 32
- 239000000126 substance Substances 0.000 claims description 32
- 230000031709 bromination Effects 0.000 claims description 30
- 229910000042 hydrogen bromide Inorganic materials 0.000 claims description 24
- 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 claims description 18
- 238000010438 heat treatment Methods 0.000 claims description 18
- 238000010531 catalytic reduction reaction Methods 0.000 claims description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 14
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 11
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 11
- 239000011736 potassium bicarbonate Substances 0.000 claims description 11
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical group [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 11
- 239000011261 inert gas Substances 0.000 claims description 8
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 7
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 claims description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 5
- 230000008030 elimination Effects 0.000 claims description 5
- 238000003379 elimination reaction Methods 0.000 claims description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- 235000011181 potassium carbonates Nutrition 0.000 claims description 3
- GIVOWRNJEIBODH-UHFFFAOYSA-N 2-(4-benzylpiperidin-1-yl)propan-1-ol Chemical compound C1CN(C(CO)C)CCC1CC1=CC=CC=C1 GIVOWRNJEIBODH-UHFFFAOYSA-N 0.000 claims description 2
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 241000212342 Sium Species 0.000 claims description 2
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 claims description 2
- 239000000347 magnesium hydroxide Substances 0.000 claims description 2
- 229910001862 magnesium hydroxide Inorganic materials 0.000 claims description 2
- 239000001632 sodium acetate Substances 0.000 claims description 2
- 235000017281 sodium acetate Nutrition 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims 1
- 150000007513 acids Chemical class 0.000 claims 1
- 125000001931 aliphatic group Chemical group 0.000 claims 1
- 239000003610 charcoal Substances 0.000 claims 1
- 235000012254 magnesium hydroxide Nutrition 0.000 claims 1
- 229910052697 platinum Inorganic materials 0.000 claims 1
- 235000017550 sodium carbonate Nutrition 0.000 claims 1
- 150000002170 ethers Chemical class 0.000 abstract description 3
- 229920006395 saturated elastomer Polymers 0.000 abstract 1
- 239000013078 crystal Substances 0.000 description 170
- 239000012295 chemical reaction liquid Substances 0.000 description 97
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 78
- 229910052794 bromium Inorganic materials 0.000 description 78
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 77
- 238000003756 stirring Methods 0.000 description 75
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 48
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 36
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 34
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- 229910052739 hydrogen Inorganic materials 0.000 description 32
- 239000001257 hydrogen Substances 0.000 description 31
- 229910052757 nitrogen Inorganic materials 0.000 description 29
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 26
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- 239000003054 catalyst Substances 0.000 description 24
- 239000000706 filtrate Substances 0.000 description 22
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 15
- 229910003446 platinum oxide Inorganic materials 0.000 description 15
- 239000007787 solid Substances 0.000 description 15
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 14
- 238000009833 condensation Methods 0.000 description 14
- 230000005494 condensation Effects 0.000 description 14
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 238000006722 reduction reaction Methods 0.000 description 11
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 10
- 239000003153 chemical reaction reagent Substances 0.000 description 10
- 239000005909 Kieselgur Substances 0.000 description 9
- 125000003118 aryl group Chemical group 0.000 description 9
- 238000005574 benzylation reaction Methods 0.000 description 9
- 239000012043 crude product Substances 0.000 description 9
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 9
- 238000000921 elemental analysis Methods 0.000 description 9
- 238000006482 condensation reaction Methods 0.000 description 8
- 238000001103 continuous-wave nuclear magnetic resonance spectrum Methods 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- 238000004809 thin layer chromatography Methods 0.000 description 8
- 238000001816 cooling Methods 0.000 description 7
- 238000012856 packing Methods 0.000 description 7
- 239000003208 petroleum Substances 0.000 description 7
- WLVPRARCUSRDNI-UHFFFAOYSA-N 2-hydroxy-1-phenyl-1-propanone Chemical compound CC(O)C(=O)C1=CC=CC=C1 WLVPRARCUSRDNI-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 239000007859 condensation product Substances 0.000 description 6
- 238000005984 hydrogenation reaction Methods 0.000 description 6
- 229940040526 anhydrous sodium acetate Drugs 0.000 description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- 238000011282 treatment Methods 0.000 description 5
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 239000012467 final product Substances 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 3
- 239000007810 chemical reaction solvent Substances 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 229910001873 dinitrogen Inorganic materials 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 239000012452 mother liquor Substances 0.000 description 3
- 238000006386 neutralization reaction Methods 0.000 description 3
- KRIOVPPHQSLHCZ-UHFFFAOYSA-N propiophenone Chemical compound CCC(=O)C1=CC=CC=C1 KRIOVPPHQSLHCZ-UHFFFAOYSA-N 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- YLJDSYYCRXITBF-UHFFFAOYSA-N 1-phenyl-2-phenylmethoxypropan-1-one Chemical compound C=1C=CC=CC=1C(=O)C(C)OCC1=CC=CC=C1 YLJDSYYCRXITBF-UHFFFAOYSA-N 0.000 description 2
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 2
- 239000012965 benzophenone Substances 0.000 description 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- OGFAWKRXZLGJSK-UHFFFAOYSA-N 1-(2,4-dihydroxyphenyl)-2-(4-nitrophenyl)ethanone Chemical compound OC1=CC(O)=CC=C1C(=O)CC1=CC=C([N+]([O-])=O)C=C1 OGFAWKRXZLGJSK-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 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 1
- 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 1
- 229910014033 C-OH Inorganic materials 0.000 description 1
- 229910014570 C—OH Inorganic materials 0.000 description 1
- 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
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-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
- 238000000862 absorption spectrum Methods 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
- 229940073608 benzyl chloride Drugs 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000003518 caustics Substances 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000003245 coal 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
- JGDFBJMWFLXCLJ-UHFFFAOYSA-N copper chromite Chemical compound [Cu]=O.[Cu]=O.O=[Cr]O[Cr]=O JGDFBJMWFLXCLJ-UHFFFAOYSA-N 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- POLCUAVZOMRGSN-UHFFFAOYSA-N dipropyl ether Chemical compound CCCOCCC POLCUAVZOMRGSN-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229960000204 ifenprodil tartrate Drugs 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- RPNNPZHFJPXFQS-UHFFFAOYSA-N methane;rhodium Chemical compound C.[Rh] RPNNPZHFJPXFQS-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- BASFCYQUMIYNBI-BKFZFHPZSA-N platinum-200 Chemical compound [200Pt] BASFCYQUMIYNBI-BKFZFHPZSA-N 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- UMFCIIBZHQXRCJ-NSCUHMNNSA-N trans-anol Chemical compound C\C=C\C1=CC=C(O)C=C1 UMFCIIBZHQXRCJ-NSCUHMNNSA-N 0.000 description 1
- BJAARRARQJZURR-UHFFFAOYSA-N trimethylazanium;hydroxide Chemical compound O.CN(C)C BJAARRARQJZURR-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
- C07D211/14—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Catalysts (AREA)
- Pyridine Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15811279A JPS5681560A (en) | 1979-12-07 | 1979-12-07 | Preparation of 1-(4-hydroxyphenyl)-2-(4-benzylpiperidino)-1- propanol and its addition salt |
| JP17319879A JPS5697270A (en) | 1979-12-30 | 1979-12-30 | Preparation of 2- 4-benzylpiperidino -1- 4-hydroxyphenyl -1- propanol and addition salt thereof |
| JP3822980A JPS56135469A (en) | 1980-03-27 | 1980-03-27 | Preparation of 2- 4-benzylpiperidino -1- 4-hydroxyphenyl -1- propanol and addition salt thereof |
| 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 |
|---|---|
| FR2471374A1 true FR2471374A1 (fr) | 1981-06-19 |
| FR2471374B1 FR2471374B1 (en, 2012) | 1984-03-09 |
Family
ID=27460552
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FR8025923A Granted 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 |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US4377691A (en, 2012) |
| AR (1) | AR229157A1 (en, 2012) |
| AT (1) | AT374181B (en, 2012) |
| BR (1) | BR8008020A (en, 2012) |
| CA (1) | CA1141387A (en, 2012) |
| CH (1) | CH648550A5 (en, 2012) |
| DE (1) | DE3045916A1 (en, 2012) |
| ES (1) | ES497527A0 (en, 2012) |
| FR (1) | FR2471374A1 (en, 2012) |
| GB (1) | GB2067187B (en, 2012) |
| IT (1) | IT1148744B (en, 2012) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2534580A1 (fr) * | 1982-10-13 | 1984-04-20 | Synthelabo | Derives de phenyl-1 piperidino-2 propanol, leur preparation, et medicaments qui les contiennent |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5364943A (en) * | 1991-11-27 | 1994-11-15 | Pfizer Inc. | Preparation of substituted piperidines |
| CN101100453B (zh) * | 2006-07-07 | 2010-05-12 | 石药集团中奇制药技术（石家庄）有限公司 | 一种酒石酸艾芬地尔合成方法 |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR5733M (en, 2012) * | 1966-09-27 | 1968-01-22 | ||
| FR2070102A1 (en) * | 1969-10-01 | 1971-09-10 | Continental Pharma | 1 subst phenyl 2 amino ethanols useful as beta - adrenergic agents peripheral vasodilators and hypo- |
| FR2105119A1 (en) * | 1970-09-29 | 1972-04-28 | Synthelabo | Analgesic piperidino ethanol deriv - 1-parabenzyloxyphenyl -2-4-benzylpiperidinoethanol |
| FR2208901A1 (en) * | 1972-12-04 | 1974-06-28 | Rhone Poulenc Sa | Alpha-(4-substd pyridino)-4-benzyloxypropiophenones - as inters for cardiovascular 1-(4-hydroxy-phenyl)-2-(4-substd piperidino) propan-1-ols |
| JPS5643266A (en) * | 1979-09-17 | 1981-04-21 | Iwaki Seiyaku Kk | Production of piperidinopropanol derivative |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2695919A (en) * | 1952-04-30 | 1954-11-30 | Upjohn Co | Aminoalcohols |
-
1980
- 1980-12-03 GB GB8038771A patent/GB2067187B/en not_active Expired
- 1980-12-04 CA CA000366167A patent/CA1141387A/en not_active Expired
- 1980-12-04 US US06/213,033 patent/US4377691A/en not_active Expired - Lifetime
- 1980-12-05 FR FR8025923A patent/FR2471374A1/fr active Granted
- 1980-12-05 ES ES497527A patent/ES497527A0/es active Granted
- 1980-12-05 DE DE19803045916 patent/DE3045916A1/de active Granted
- 1980-12-05 IT IT26487/80A patent/IT1148744B/it active
- 1980-12-05 AR AR283504A patent/AR229157A1/es active
- 1980-12-08 CH CH9032/80A patent/CH648550A5/de not_active IP Right Cessation
- 1980-12-08 BR BR8008020A patent/BR8008020A/pt unknown
- 1980-12-09 AT AT0597580A patent/AT374181B/de active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR5733M (en, 2012) * | 1966-09-27 | 1968-01-22 | ||
| FR2070102A1 (en) * | 1969-10-01 | 1971-09-10 | Continental Pharma | 1 subst phenyl 2 amino ethanols useful as beta - adrenergic agents peripheral vasodilators and hypo- |
| FR2105119A1 (en) * | 1970-09-29 | 1972-04-28 | Synthelabo | Analgesic piperidino ethanol deriv - 1-parabenzyloxyphenyl -2-4-benzylpiperidinoethanol |
| FR2208901A1 (en) * | 1972-12-04 | 1974-06-28 | Rhone Poulenc Sa | Alpha-(4-substd pyridino)-4-benzyloxypropiophenones - as inters for cardiovascular 1-(4-hydroxy-phenyl)-2-(4-substd piperidino) propan-1-ols |
| JPS5643266A (en) * | 1979-09-17 | 1981-04-21 | Iwaki Seiyaku Kk | Production of piperidinopropanol derivative |
Non-Patent Citations (3)
| Title |
|---|
| CA1981 * |
| EXBK/44 * |
| EXBK/56 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2534580A1 (fr) * | 1982-10-13 | 1984-04-20 | Synthelabo | Derives de phenyl-1 piperidino-2 propanol, leur preparation, et medicaments qui les contiennent |
| EP0109317A3 (en) * | 1982-10-13 | 1984-08-08 | Synthelabo | Phenyl-1-piperidino-2-propanol derivatives, their preparation and medicaments containing them |
Also Published As
| Publication number | Publication date |
|---|---|
| CA1141387A (en) | 1983-02-15 |
| DE3045916C2 (en, 2012) | 1989-11-30 |
| US4377691A (en) | 1983-03-22 |
| IT1148744B (it) | 1986-12-03 |
| AT374181B (de) | 1984-03-26 |
| AR229157A1 (es) | 1983-06-30 |
| ATA597580A (de) | 1983-08-15 |
| ES8200342A1 (es) | 1981-11-01 |
| GB2067187A (en) | 1981-07-22 |
| ES497527A0 (es) | 1981-11-01 |
| IT8026487A0 (it) | 1980-12-05 |
| GB2067187B (en) | 1983-11-30 |
| BR8008020A (pt) | 1981-06-23 |
| DE3045916A1 (de) | 1981-09-03 |
| CH648550A5 (de) | 1985-03-29 |
| FR2471374B1 (en, 2012) | 1984-03-09 |
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| TP | Transmission of property | ||
| ST | Notification of lapse |