Pharmacology – OPIOIDS (MADE EASY)
Pharmacology – OPIOIDS (MADE EASY)

WO2009003271A1 – Conversion of thebaine to morphine derivatives – Google Patents

Conversion of thebaine to morphine derivatives Download PDF

Info

Publication number
WO2009003271A1 WO2009003271A1 PCT/CA2008/001178 CA2008001178W WO2009003271A1 WO 2009003271 A1 WO2009003271 A1 WO 2009003271A1 CA 2008001178 W CA2008001178 W CA 2008001178W WO 2009003271 A1 WO2009003271 A1 WO 2009003271A1
Authority
WO
WIPO (PCT)
Prior art keywords
thebaine
ketal
derivative
catalyst
hydrocodone
Prior art date

Links

  • FQXXSQDCDRQNQE-VMDGZTHMSA-N Thebaine Chemical compound C([C@@H](N(CC1)C)C2=CC=C3OC)C4=CC=C(OC)C5=C4[C@@]21[C@H]3O5 FQXXSQDCDRQNQE-VMDGZTHMSA-N 0.000 title claims abstract description 67
  • 229930003945 thebaine Natural products 0.000 title claims abstract description 65
  • 238000006243 chemical reaction Methods 0.000 title claims abstract description 30
  • BQJCRHHNABKAKU-KBQPJGBKSA-N Morphine Chemical class O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 title claims abstract description 25
  • LLPOLZWFYMWNKH-CMKMFDCUSA-N Hydrocodone Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)CC(=O)[C@@H]1OC1=C2C3=CC=C1OC LLPOLZWFYMWNKH-CMKMFDCUSA-N 0.000 claims abstract description 48
  • 229960000240 hydrocodone Drugs 0.000 claims abstract description 42
  • 239000003054 catalyst Substances 0.000 claims abstract description 33
  • 238000005580 one pot reaction Methods 0.000 claims abstract description 17
  • 238000000034 method Methods 0.000 claims abstract description 10
  • 239000002253 acid Substances 0.000 claims abstract description 6
  • 229910052751 metal Inorganic materials 0.000 claims abstract description 5
  • 239000002184 metal Substances 0.000 claims abstract description 5
  • LYCAIKOWRPUZTN-UHFFFAOYSA-N glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 24
  • KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 22
  • 150000002894 organic compounds Chemical class 0.000 claims description 18
  • 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
  • OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 16
  • 238000005984 hydrogenation reaction Methods 0.000 claims description 15
  • 229910052763 palladium Inorganic materials 0.000 claims description 13
  • LXNAVEXFUKBNMK-UHFFFAOYSA-N acetic acid;palladium Chemical compound [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 claims description 11
  • BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 11
  • 238000006460 hydrolysis reaction Methods 0.000 claims description 10
  • WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 9
  • BRUQQQPBMZOVGD-XFKAJCMBSA-N Oxycontin Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(OC)C2=C5[C@@]13CCN4C BRUQQQPBMZOVGD-XFKAJCMBSA-N 0.000 claims description 8
  • RIOQSEWOXXDEQQ-UHFFFAOYSA-N Triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 8
  • 125000000217 alkyl group Chemical group 0.000 claims description 8
  • UFHFLCQGNIYNRP-UHFFFAOYSA-N hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
  • 229960002085 oxycodone Drugs 0.000 claims description 8
  • 229910052697 platinum Inorganic materials 0.000 claims description 8
  • -1 RhCI3 Inorganic materials 0.000 claims description 7
  • GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 7
  • WKBOTKDWSSQWDR-UHFFFAOYSA-N bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 7
  • 229910052739 hydrogen Inorganic materials 0.000 claims description 7
  • 239000001257 hydrogen Substances 0.000 claims description 7
  • 150000001875 compounds Chemical class 0.000 claims description 6
  • LJVKMVSYTWPNGA-UUWFMWQGSA-N neopinone Chemical compound O=C([C@@H]1O2)CC=C3[C@H]4CC5=CC=C(OC)C2=C5[C@@]13CCN4C LJVKMVSYTWPNGA-UUWFMWQGSA-N 0.000 claims description 6
  • WVLOADHCBXTIJK-YNHQPCIGSA-N Hydromorphone Chemical compound O([C@H]1C(CC[C@H]23)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O WVLOADHCBXTIJK-YNHQPCIGSA-N 0.000 claims description 5
  • UQCNKQCJZOAFTQ-ISWURRPUSA-N Oxymorphone Chemical compound O([C@H]1C(CC[C@]23O)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O UQCNKQCJZOAFTQ-ISWURRPUSA-N 0.000 claims description 5
  • 229910052799 carbon Inorganic materials 0.000 claims description 5
  • 229910052736 halogen Inorganic materials 0.000 claims description 5
  • 150000002367 halogens Chemical class 0.000 claims description 5
  • 229960001410 hydromorphone Drugs 0.000 claims description 5
  • 229960005118 oxymorphone Drugs 0.000 claims description 5
  • YKIOKAURTKXMSB-UHFFFAOYSA-N Adams’s catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 claims description 4
  • UZHSEJADLWPNLE-GRGSLBFTSA-N Naloxone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(O)C2=C5[C@@]13CCN4CC=C UZHSEJADLWPNLE-GRGSLBFTSA-N 0.000 claims description 4
  • 229960004127 Naloxone Drugs 0.000 claims description 4
  • DQCKKXVULJGBQN-XFWGSAIBSA-N Naltrexone Chemical compound N1([C@@H]2CC3=CC=C(C=4O[C@@H]5[C@](C3=4)([C@]2(CCC5=O)O)CC1)O)CC1CC1 DQCKKXVULJGBQN-XFWGSAIBSA-N 0.000 claims description 4
  • 229960003086 Naltrexone Drugs 0.000 claims description 4
  • 229910002674 PdO Inorganic materials 0.000 claims description 4
  • 229910019020 PtO2 Inorganic materials 0.000 claims description 4
  • 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 4
  • 125000005210 alkyl ammonium group Chemical group 0.000 claims description 4
  • 229910052801 chlorine Inorganic materials 0.000 claims description 4
  • 239000000460 chlorine Substances 0.000 claims description 4
  • 150000002009 diols Chemical class 0.000 claims description 4
  • 229910052740 iodine Inorganic materials 0.000 claims description 4
  • 229910052741 iridium Inorganic materials 0.000 claims description 4
  • 229910052703 rhodium Inorganic materials 0.000 claims description 4
  • 229910052707 ruthenium Inorganic materials 0.000 claims description 4
  • 229910052782 aluminium Inorganic materials 0.000 claims description 3
  • 229910052803 cobalt Inorganic materials 0.000 claims description 3
  • 229910052802 copper Inorganic materials 0.000 claims description 3
  • 229910052742 iron Inorganic materials 0.000 claims description 3
  • 229910052759 nickel Inorganic materials 0.000 claims description 3
  • JOXIMZWYDAKGHI-UHFFFAOYSA-N p-toluenesulfonic acid Substances CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 3
  • 150000003839 salts Chemical class 0.000 claims description 3
  • 239000011780 sodium chloride Substances 0.000 claims description 3
  • 229910052718 tin Inorganic materials 0.000 claims description 3
  • 229910052723 transition metal Inorganic materials 0.000 claims description 3
  • 150000003624 transition metals Chemical class 0.000 claims description 3
  • 229910052725 zinc Inorganic materials 0.000 claims description 3
  • SKQUTIPQJKQFRA-UHFFFAOYSA-N 2,3-dimethylbutane-1,4-diol Chemical compound OCC(C)C(C)CO SKQUTIPQJKQFRA-UHFFFAOYSA-N 0.000 claims description 2
  • 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
  • 229950004155 Etorphine Drugs 0.000 claims description 2
  • 239000002841 Lewis acid Substances 0.000 claims description 2
  • 229960000805 Nalbuphine Drugs 0.000 claims description 2
  • NETZHAKZCGBWSS-CEDHKZHLSA-N Nalbuphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]1(O)CC[C@@H]3O)CN2CC1CCC1 NETZHAKZCGBWSS-CEDHKZHLSA-N 0.000 claims description 2
  • 125000002252 acyl group Chemical group 0.000 claims description 2
  • 229910052794 bromium Inorganic materials 0.000 claims description 2
  • RMRJXGBAOAMLHD-CTAPUXPBSA-N buprenorphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]11CC[C@@]3([C@H](C1)[C@](C)(O)C(C)(C)C)OC)CN2CC1CC1 RMRJXGBAOAMLHD-CTAPUXPBSA-N 0.000 claims description 2
  • 229960001736 buprenorphine Drugs 0.000 claims description 2
  • 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
  • ZAMOUSCENKQFHK-UHFFFAOYSA-N chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
  • 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 claims description 2
  • 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 2
  • QRHQPCRIZNMZIZ-MASJHSKDSA-N etorphine Chemical compound O([C@H]1[C@@]2(OC)C=C[C@@]34C[C@@H]2[C@](C)(O)CCC)C2=CC=CC5=C2[C@]41CCN(C)[C@@H]3C5 QRHQPCRIZNMZIZ-MASJHSKDSA-N 0.000 claims description 2
  • 229910052731 fluorine Inorganic materials 0.000 claims description 2
  • 230000003301 hydrolyzing Effects 0.000 claims description 2
  • 239000011630 iodine Substances 0.000 claims description 2
  • PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
  • 229910052745 lead Inorganic materials 0.000 claims description 2
  • 150000007517 lewis acids Chemical class 0.000 claims description 2
  • 229910052757 nitrogen Inorganic materials 0.000 claims description 2
  • 230000003647 oxidation Effects 0.000 claims description 2
  • 238000007254 oxidation reaction Methods 0.000 claims description 2
  • 229910052760 oxygen Inorganic materials 0.000 claims description 2
  • 125000005489 p-toluenesulfonic acid group Chemical group 0.000 claims description 2
  • 125000004368 propenyl group Chemical group C(=CC)* 0.000 claims description 2
  • DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 2
  • 229910052717 sulfur Inorganic materials 0.000 claims description 2
  • 239000000543 intermediate Substances 0.000 abstract description 27
  • 238000004519 manufacturing process Methods 0.000 description 12
  • 229930013930 alkaloids Natural products 0.000 description 6
  • BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
  • VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
  • 238000003786 synthesis reaction Methods 0.000 description 6
  • 0 *C1=CC=C(C(Cc2ccc3*)*CC4)[C@]44c2c3O[C@]14 Chemical compound *C1=CC=C(C(Cc2ccc3*)*CC4)[C@]44c2c3O[C@]14 0.000 description 5
  • VHUUQVKOLVNVRT-UHFFFAOYSA-N ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
  • 230000015572 biosynthetic process Effects 0.000 description 5
  • 150000002576 ketones Chemical class 0.000 description 5
  • 229960005181 morphine Drugs 0.000 description 5
  • 229930014694 morphine Natural products 0.000 description 5
  • 239000000047 product Substances 0.000 description 5
  • 230000002194 synthesizing Effects 0.000 description 5
  • 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 4
  • 238000005160 1H NMR spectroscopy Methods 0.000 description 4
  • OROGSEYTTFOCAN-DNJOTXNNSA-N Codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 4
  • 239000007832 Na2SO4 Substances 0.000 description 4
  • 150000003797 alkaloid derivatives Chemical class 0.000 description 4
  • HEDRZPFGACZZDS-UHFFFAOYSA-N chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
  • 239000011541 reaction mixture Substances 0.000 description 4
  • 229910052938 sodium sulfate Inorganic materials 0.000 description 4
  • 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 3
  • 238000004440 column chromatography Methods 0.000 description 3
  • 238000001914 filtration Methods 0.000 description 3
  • 229910000027 potassium carbonate Inorganic materials 0.000 description 3
  • 239000000377 silicon dioxide Substances 0.000 description 3
  • 241000196324 Embryophyta Species 0.000 description 2
  • 229920000126 Latex Polymers 0.000 description 2
  • 240000001090 Papaver somniferum Species 0.000 description 2
  • 230000035969 Vmax Effects 0.000 description 2
  • VTYYLEPIZMXCLO-UHFFFAOYSA-L calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
  • 239000003795 chemical substances by application Substances 0.000 description 2
  • 229960004126 codeine Drugs 0.000 description 2
  • 239000000470 constituent Substances 0.000 description 2
  • 230000000875 corresponding Effects 0.000 description 2
  • 239000000284 extract Substances 0.000 description 2
  • 238000002955 isolation Methods 0.000 description 2
  • 239000004816 latex Substances 0.000 description 2
  • 235000006502 papoula Nutrition 0.000 description 2
  • OZAIFHULBGXAKX-UHFFFAOYSA-N precursor Substances N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 2
  • 238000000746 purification Methods 0.000 description 2
  • 239000007858 starting material Substances 0.000 description 2
  • RVJQWONQPCTLDL-SEYRRXLCSA-N (4R,4aR,7aR,12bS)-7,9-dimethoxy-3-methyl-2,4,4a,5,6,7,7a,13-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline Chemical compound C([C@@H](N(CC1)C)[C@@H]2CCC3OC)C4=CC=C(OC)C5=C4[C@@]21[C@H]3O5 RVJQWONQPCTLDL-SEYRRXLCSA-N 0.000 description 1
  • XJZOLKDBHJPTAT-ATNYCFDYSA-N (4R,4aR,7aR,12bS)-7,9-dimethoxy-3-methyl-2,4,4a,5,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline Chemical compound C([C@@H](N(CC1)C)[C@@H]2CC=C3OC)C4=CC=C(OC)C5=C4[C@@]21[C@H]3O5 XJZOLKDBHJPTAT-ATNYCFDYSA-N 0.000 description 1
  • YYCRAERBSFHMPL-FSFXSCMFSA-N (4R,4aS,12bS)-4a-hydroxy-9-methoxy-3-methyl-2,4,7a,13-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-7-one Chemical compound O1C2C(=O)C=C[C@@]3(O)[C@H]4CC5=CC=C(OC)C1=C5[C@@]23CCN4C YYCRAERBSFHMPL-FSFXSCMFSA-N 0.000 description 1
  • 150000000180 1,2-diols Chemical class 0.000 description 1
  • PNEYBMLMFCGWSK-UHFFFAOYSA-N AI2O3 Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
  • RWCCWEUUXYIKHB-UHFFFAOYSA-N Benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 1
  • 239000004215 Carbon black (E152) Substances 0.000 description 1
  • XYYVYLMBEZUESM-CMKMFDCUSA-N Codeinone Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=CC(=O)[C@@H]1OC1=C2C3=CC=C1OC XYYVYLMBEZUESM-CMKMFDCUSA-N 0.000 description 1
  • RBOXVHNMENFORY-DNJOTXNNSA-N Dihydrocodeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC RBOXVHNMENFORY-DNJOTXNNSA-N 0.000 description 1
  • SWIRXSKBBSJXGY-SBBZOCNPSA-N Oc1ccc(CC2NCC[C@]34C2CC2)c3c1O[C@H]4C2=O Chemical compound Oc1ccc(CC2NCC[C@]34C2CC2)c3c1O[C@H]4C2=O SWIRXSKBBSJXGY-SBBZOCNPSA-N 0.000 description 1
  • GEHJYWRUCIMESM-UHFFFAOYSA-L Sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 1
  • QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
  • RRJQTGHQFYTZOW-ILWKUFEGSA-N Thebacon Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)C=C(OC(C)=O)[C@@H]1OC1=C2C3=CC=C1OC RRJQTGHQFYTZOW-ILWKUFEGSA-N 0.000 description 1
  • 229960004412 Thebacon Drugs 0.000 description 1
  • 239000003377 acid catalyst Substances 0.000 description 1
  • 238000007792 addition Methods 0.000 description 1
  • 150000001336 alkenes Chemical group 0.000 description 1
  • 239000000908 ammonium hydroxide Substances 0.000 description 1
  • 239000011260 aqueous acid Substances 0.000 description 1
  • 230000002051 biphasic Effects 0.000 description 1
  • 229910000019 calcium carbonate Inorganic materials 0.000 description 1
  • 230000003197 catalytic Effects 0.000 description 1
  • 238000004587 chromatography analysis Methods 0.000 description 1
  • 229910052681 coesite Inorganic materials 0.000 description 1
  • 229910052906 cristobalite Inorganic materials 0.000 description 1
  • 239000012043 crude product Substances 0.000 description 1
  • 229960000920 dihydrocodeine Drugs 0.000 description 1
  • 239000003814 drug Substances 0.000 description 1
  • 238000001035 drying Methods 0.000 description 1
  • 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
  • LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
  • IMROMDMJAWUWLK-UHFFFAOYSA-N ethenol Chemical compound OC=C IMROMDMJAWUWLK-UHFFFAOYSA-N 0.000 description 1
  • 238000000605 extraction Methods 0.000 description 1
  • 238000007306 functionalization reaction Methods 0.000 description 1
  • 150000002430 hydrocarbons Chemical class 0.000 description 1
  • 239000012535 impurity Substances 0.000 description 1
  • 239000000463 material Substances 0.000 description 1
  • 238000002156 mixing Methods 0.000 description 1
  • 239000000203 mixture Substances 0.000 description 1
  • 230000004048 modification Effects 0.000 description 1
  • 238000006011 modification reaction Methods 0.000 description 1
  • 108010053700 morphinone reductase Proteins 0.000 description 1
  • 230000003533 narcotic Effects 0.000 description 1
  • 230000003364 opioid Effects 0.000 description 1
  • 239000012044 organic layer Substances 0.000 description 1
  • 229910052762 osmium Inorganic materials 0.000 description 1
  • 239000000825 pharmaceutical preparation Substances 0.000 description 1
  • ZLMJMSJWJFRBEC-UHFFFAOYSA-N potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
  • 229910052700 potassium Inorganic materials 0.000 description 1
  • 239000011591 potassium Substances 0.000 description 1
  • 229910052904 quartz Inorganic materials 0.000 description 1
  • 238000010992 reflux Methods 0.000 description 1
  • 238000010898 silica gel chromatography Methods 0.000 description 1
  • 239000007787 solid Substances 0.000 description 1
  • 239000002904 solvent Substances 0.000 description 1
  • 241000894007 species Species 0.000 description 1
  • 238000003756 stirring Methods 0.000 description 1
  • 229910052682 stishovite Inorganic materials 0.000 description 1
  • 238000006467 substitution reaction Methods 0.000 description 1
  • 229910052905 tridymite Inorganic materials 0.000 description 1

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D489/00—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula:
    • C07D489/02—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: with oxygen atoms attached in positions 3 and 6, e.g. morphine, morphinone

Abstract

Description

Claims

Priority Applications (6)

Application Number Priority Date Filing Date Title
JP2010513589A JP2010531813A (en) 2007-06-29 2008-06-30 Conversion of thebaine to morphine derivatives.
CA2692429A CA2692429C (en) 2007-06-29 2008-06-30 Conversion of thebaine to morphine derivatives
MX2010000162A MX2010000162A (en) 2007-06-29 2008-06-30 Conversion of thebaine to morphine derivatives.
AU2008271863A AU2008271863A1 (en) 2007-06-29 2008-06-30 Conversion of thebaine to morphine derivatives
EP08772838A EP2173754A1 (en) 2007-06-29 2008-06-30 Conversion of thebaine to morphine derivatives
CN200880022624A CN101801976A (en) 2007-06-29 2008-06-30 Conversion of thebaine to morphine derivatives

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US11/771,259 2007-06-29
US11/771,259 US7928234B2 (en) 2007-06-29 2007-06-29 Conversion of thebaine to morphine derivatives

Publications (1)

Publication Number Publication Date
WO2009003271A1 true WO2009003271A1 (en) 2009-01-08

Family

ID=40161386

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CA2008/001178 WO2009003271A1 (en) 2007-06-29 2008-06-30 Conversion of thebaine to morphine derivatives

Country Status (9)

Country Link
US (1) US7928234B2 (en)
EP (1) EP2173754A1 (en)
JP (1) JP2010531813A (en)
KR (1) KR20100055393A (en)
CN (1) CN101801976A (en)
AU (1) AU2008271863A1 (en)
CA (1) CA2692429C (en)
MX (1) MX2010000162A (en)
WO (1) WO2009003271A1 (en)

Cited By (4)

Publication number Priority date Publication date Assignee Title
US8846923B1 (en) 2013-12-18 2014-09-30 Cody Laboratories, Inc. Preparation of 14-hydroxycodeinone sulfate
WO2015069717A1 (en) 2013-11-07 2015-05-14 Mallinckrodt Llc Production of 6-hydroxy morphinans without the isolation of intermediates
US9062062B1 (en) 2013-12-18 2015-06-23 Cody Laboratories, Inc. Synthesis of oxycodone hydrochloride
US10227354B2 (en) 2013-12-18 2019-03-12 Cody Laboratories, Inc. Conversion of oxycodone base to oxycodone hydrochloride

Families Citing this family (6)

Publication number Priority date Publication date Assignee Title
IN2014CN03197A (en) * 2011-10-03 2015-07-03 Matthey Plc Johnson
EP2970320B1 (en) 2013-03-15 2020-10-28 Johnson Matthey Public Limited Company Morphine sulfate methanolic solvate, processes for making same and related compositions and methods for treating pain
WO2015015146A1 (en) * 2013-08-02 2015-02-05 Johnson Matthey Public Limited Company Process for the preparation of oxymorphone
CA2881229C (en) 2014-02-07 2022-04-05 Tomas Hudlicky Methods for the preparation of hydromorphone
US10081636B2 (en) 2016-07-08 2018-09-25 Cody Laboratories, Inc. Method for catalytic preparation of hydromorphone, hydrocodone, and other opiates
CN113845526B (en) * 2021-01-18 2022-11-08 四川大学 Thebaine derivative and preparation method and application thereof

Citations (3)

Publication number Priority date Publication date Assignee Title
US4277604A (en) * 1980-01-25 1981-07-07 The United States Of America As Represented By The Department Of Health And Human Services Facile synthesis of codeine precursors from thebaine
US5668285A (en) * 1986-10-31 1997-09-16 The United States Of America As Represented By The Department Of Health And Human Services Total synthesis of northebaine, normophine, noroxymorphone enantiomers and derivatives via N-Nor intermediates
WO2006138020A2 (en) * 2005-06-16 2006-12-28 Mallinckrodt Inc. A synthetic route to 14-hydroxyl opiates through 1-halo-thebaine or analogs
  • 2007

    • 2007-06-29 US US11/771,259 patent/US7928234B2/en not_active Expired – Fee Related
  • 2008

    • 2008-06-30 KR KR1020107002072A patent/KR20100055393A/en not_active Application Discontinuation
    • 2008-06-30 AU AU2008271863A patent/AU2008271863A1/en not_active Abandoned
    • 2008-06-30 MX MX2010000162A patent/MX2010000162A/en not_active Application Discontinuation
    • 2008-06-30 JP JP2010513589A patent/JP2010531813A/en active Pending
    • 2008-06-30 CN CN200880022624A patent/CN101801976A/en active Pending
    • 2008-06-30 WO PCT/CA2008/001178 patent/WO2009003271A1/en active Application Filing
    • 2008-06-30 CA CA2692429A patent/CA2692429C/en active Active
    • 2008-06-30 EP EP08772838A patent/EP2173754A1/en not_active Withdrawn

Patent Citations (3)

Publication number Priority date Publication date Assignee Title
US4277604A (en) * 1980-01-25 1981-07-07 The United States Of America As Represented By The Department Of Health And Human Services Facile synthesis of codeine precursors from thebaine
US5668285A (en) * 1986-10-31 1997-09-16 The United States Of America As Represented By The Department Of Health And Human Services Total synthesis of northebaine, normophine, noroxymorphone enantiomers and derivatives via N-Nor intermediates
WO2006138020A2 (en) * 2005-06-16 2006-12-28 Mallinckrodt Inc. A synthetic route to 14-hydroxyl opiates through 1-halo-thebaine or analogs

Non-Patent Citations (2)

Title
BARBER R.B. ET AL.: “Conversion of Thebaine to Codeine”, J. MED. CHEM., vol. 19, no. 10, 1996, pages 1175 – 1180, XP008129065 *
OSA Y. ET AL.: “A New Useful Conversion Method of Naltrexone to 14-Deoxynaltrexone”, HETEROCYCLES, vol. 69, 2006, pages 271 – 282, XP008129079 *

Cited By (10)

Publication number Priority date Publication date Assignee Title
WO2015069717A1 (en) 2013-11-07 2015-05-14 Mallinckrodt Llc Production of 6-hydroxy morphinans without the isolation of intermediates
EP3065743A1 (en) * 2013-11-07 2016-09-14 Mallinckrodt LLC Production of 6-hydroxy morphinans without the isolation of intermediates
EP3065743A4 (en) * 2013-11-07 2017-04-05 Mallinckrodt LLC Production of 6-hydroxy morphinans without the isolation of intermediates
US8846923B1 (en) 2013-12-18 2014-09-30 Cody Laboratories, Inc. Preparation of 14-hydroxycodeinone sulfate
US9062062B1 (en) 2013-12-18 2015-06-23 Cody Laboratories, Inc. Synthesis of oxycodone hydrochloride
US9090620B2 (en) 2013-12-18 2015-07-28 Cody Laboratories, Inc. Preparation of 14-hydroxycodeinone sulfate
US9108976B2 (en) 2013-12-18 2015-08-18 Cody Laboratories, Inc. Preparation of 14-hydroxycodeinone sulfate
US9233972B2 (en) 2013-12-18 2016-01-12 Cody Laboratories, Inc. Preparation of 14-hydroxycodeinone sulfate
US9309257B2 (en) 2013-12-18 2016-04-12 Cody Laboratories, Inc. Preparation of oxycodone base form 14-hydroxycodeinone sulfate
US10227354B2 (en) 2013-12-18 2019-03-12 Cody Laboratories, Inc. Conversion of oxycodone base to oxycodone hydrochloride

Also Published As

Publication number Publication date
JP2010531813A (en) 2010-09-30
CN101801976A (en) 2010-08-11
CA2692429A1 (en) 2009-01-08
CA2692429C (en) 2017-03-21
EP2173754A1 (en) 2010-04-14
US7928234B2 (en) 2011-04-19
US20090005563A1 (en) 2009-01-01
AU2008271863A1 (en) 2009-01-08
KR20100055393A (en) 2010-05-26
MX2010000162A (en) 2010-03-22

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