AU2003279287B2 - Preparation of codeine from morphine - Google Patents
Preparation of codeine from morphine Download PDFInfo
- Publication number
- AU2003279287B2 AU2003279287B2 AU2003279287A AU2003279287A AU2003279287B2 AU 2003279287 B2 AU2003279287 B2 AU 2003279287B2 AU 2003279287 A AU2003279287 A AU 2003279287A AU 2003279287 A AU2003279287 A AU 2003279287A AU 2003279287 B2 AU2003279287 B2 AU 2003279287B2
- Authority
- AU
- Australia
- Prior art keywords
- codeine
- hydrocarbon solvent
- reaction mixture
- set forth
- approximately
- 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.)
- Ceased
Links
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound 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 75
- 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 title claims abstract description 58
- 229960004126 codeine Drugs 0.000 title claims abstract description 48
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 title claims abstract description 48
- 229960005181 morphine Drugs 0.000 title claims abstract description 38
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- 238000000034 method Methods 0.000 claims abstract description 30
- 239000011541 reaction mixture Substances 0.000 claims abstract description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 24
- 239000004215 Carbon black (E152) Substances 0.000 claims abstract description 22
- 229930195733 hydrocarbon Natural products 0.000 claims abstract description 22
- 150000002430 hydrocarbons Chemical class 0.000 claims abstract description 22
- 239000002904 solvent Substances 0.000 claims abstract description 22
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 claims abstract description 16
- 238000006243 chemical reaction Methods 0.000 claims abstract description 10
- 238000010992 reflux Methods 0.000 claims abstract description 10
- 239000012022 methylating agents Substances 0.000 claims abstract description 8
- 229910052500 inorganic mineral Inorganic materials 0.000 claims abstract description 6
- 239000011707 mineral Substances 0.000 claims abstract description 6
- 150000007522 mineralic acids Chemical class 0.000 claims abstract description 6
- 150000007524 organic acids Chemical class 0.000 claims abstract description 6
- 238000001816 cooling Methods 0.000 claims abstract description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 92
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 37
- 239000012071 phase Substances 0.000 claims description 14
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 8
- 238000000926 separation method Methods 0.000 claims description 8
- 238000007069 methylation reaction Methods 0.000 claims description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- 239000008346 aqueous phase Substances 0.000 claims description 6
- 230000000694 effects Effects 0.000 claims description 5
- ZMGDXJGLGYNTSM-UHFFFAOYSA-N ethanolate;trimethyl(phenyl)azanium Chemical group CC[O-].C[N+](C)(C)C1=CC=CC=C1 ZMGDXJGLGYNTSM-UHFFFAOYSA-N 0.000 claims description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 claims description 3
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 claims description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
- 239000008096 xylene Substances 0.000 claims description 2
- 125000003944 tolyl group Chemical group 0.000 claims 2
- XBDFUVJODXQZOR-UHFFFAOYSA-M ethanolate;trimethyl(phenyl)azanium;chloride Chemical compound [Cl-].CC[O-].C[N+](C)(C)C1=CC=CC=C1.C[N+](C)(C)C1=CC=CC=C1 XBDFUVJODXQZOR-UHFFFAOYSA-M 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 abstract description 7
- HGPQAWTZLJXCTC-SSTWWWIQSA-N (4r,4ar,7s,7ar,12bs)-7,9-dimethoxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline Chemical compound C([C@@H](N(CC1)C)[C@@H]2C=C[C@@H]3OC)C4=CC=C(OC)C5=C4[C@@]21[C@H]3O5 HGPQAWTZLJXCTC-SSTWWWIQSA-N 0.000 abstract description 6
- WRRSFOZOETZUPG-FFHNEAJVSA-N (4r,4ar,7s,7ar,12bs)-9-methoxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-7-ol;hydrate Chemical compound O.C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC WRRSFOZOETZUPG-FFHNEAJVSA-N 0.000 description 38
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000000203 mixture Substances 0.000 description 11
- 239000002002 slurry Substances 0.000 description 11
- 230000001035 methylating effect Effects 0.000 description 10
- 239000006227 byproduct Substances 0.000 description 5
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- MQAYPFVXSPHGJM-UHFFFAOYSA-M trimethyl(phenyl)azanium;chloride Chemical compound [Cl-].C[N+](C)(C)C1=CC=CC=C1 MQAYPFVXSPHGJM-UHFFFAOYSA-M 0.000 description 3
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- 238000010533 azeotropic distillation Methods 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 238000004042 decolorization Methods 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 229910021641 deionized water Inorganic materials 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000004081 narcotic agent Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 239000012429 reaction media Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 239000008896 Opium Substances 0.000 description 1
- 206010038584 Repetitive strain injury Diseases 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- -1 ethoxide anion Chemical class 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 229960001027 opium Drugs 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 239000012066 reaction slurry Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- CMQCNTNASCDNGR-UHFFFAOYSA-N toluene;hydrate Chemical compound O.CC1=CC=CC=C1 CMQCNTNASCDNGR-UHFFFAOYSA-N 0.000 description 1
- HADKRTWCOYPCPH-UHFFFAOYSA-M trimethylphenylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)C1=CC=CC=C1 HADKRTWCOYPCPH-UHFFFAOYSA-M 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10/274,702 | 2002-10-21 | ||
| US10/274,702 US6579985B1 (en) | 2002-10-21 | 2002-10-21 | Preparation of codeine from morphine |
| PCT/US2003/032698 WO2004037826A2 (en) | 2002-10-21 | 2003-10-14 | Preparation of codeine from morphine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2003279287A1 AU2003279287A1 (en) | 2004-05-13 |
| AU2003279287B2 true AU2003279287B2 (en) | 2009-01-29 |
Family
ID=23049276
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2003279287A Ceased AU2003279287B2 (en) | 2002-10-21 | 2003-10-14 | Preparation of codeine from morphine |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US6579985B1 (enExample) |
| EP (1) | EP1560833B1 (enExample) |
| JP (1) | JP2006505588A (enExample) |
| CN (1) | CN1692117A (enExample) |
| AT (1) | ATE356819T1 (enExample) |
| AU (1) | AU2003279287B2 (enExample) |
| CA (1) | CA2502935A1 (enExample) |
| DE (1) | DE60312543T2 (enExample) |
| ES (1) | ES2282689T3 (enExample) |
| MX (1) | MXPA05004162A (enExample) |
| WO (1) | WO2004037826A2 (enExample) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6949645B1 (en) | 2004-05-20 | 2005-09-27 | Acura Pharmaceuticals, Inc. | Process for the production of opiates |
| US6972332B1 (en) * | 2004-05-20 | 2005-12-06 | Acura Pharmaceuticals, Inc. | Process for the production of opiates |
| WO2008022285A1 (en) * | 2006-08-16 | 2008-02-21 | Auspex Pharmaceuticals, Inc. | Preparation and utility of opioid analgesics |
| CN105247038B (zh) * | 2013-03-15 | 2021-08-27 | 小利兰·斯坦福大学托管委员会 | 产生苄基异喹啉生物碱(bia)的微生物及其制备和使用方法 |
| CN112410379B (zh) | 2013-11-04 | 2024-12-31 | 小利兰·斯坦福大学托管委员会 | 产生苄基异喹啉生物碱(bia)前体的微生物以及制备和使用所述前体的方法 |
| JP7266966B2 (ja) | 2015-05-08 | 2023-05-01 | ザ ボード オブ トラスティーズ オブ ザ レランド スタンフォード ジュニア ユニバーシティー | エピメラーゼ及びベンジルイソキノリンアルカロイドを産生する方法 |
| CN120399912A (zh) | 2019-03-08 | 2025-08-01 | 小利兰·斯坦福大学托管委员会 | 产生莨菪烷生物碱(ta)的非植物宿主细胞及其制备和使用方法 |
| CN110261194B (zh) * | 2019-06-06 | 2022-02-22 | 深圳砺剑防卫技术有限公司 | 一种毒品探测设备校验品的制备方法及毒品探测设备校验品 |
| TR2021022252A2 (tr) * | 2021-12-31 | 2022-01-21 | Toprak Mahsulleri Ofisi Genel Mueduerluegue | Kodei̇n kamphosulfonat üreti̇mi̇ne dai̇r yeni̇ bi̇r yöntem |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0268710A1 (en) * | 1986-11-25 | 1988-06-01 | Council of Scientific and Industrial Research | Improved process for the preparation of codeine from morphine |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CS277517B6 (sk) * | 1990-12-12 | 1993-02-17 | Slovakofarma S P | Spósob čistenia kodeinu připraveného metylizáciou morfínu |
| US6204337B1 (en) * | 1996-11-19 | 2001-03-20 | The Board Of Regents Of The University And Community College System Of Neveda | Solid-phase synthesis of codeine from morphine |
-
2002
- 2002-10-21 US US10/274,702 patent/US6579985B1/en not_active Expired - Lifetime
-
2003
- 2003-10-14 MX MXPA05004162A patent/MXPA05004162A/es active IP Right Grant
- 2003-10-14 CA CA002502935A patent/CA2502935A1/en not_active Abandoned
- 2003-10-14 EP EP03770770A patent/EP1560833B1/en not_active Expired - Lifetime
- 2003-10-14 DE DE60312543T patent/DE60312543T2/de not_active Expired - Fee Related
- 2003-10-14 AT AT03770770T patent/ATE356819T1/de not_active IP Right Cessation
- 2003-10-14 JP JP2004546881A patent/JP2006505588A/ja not_active Withdrawn
- 2003-10-14 CN CN200380100724.3A patent/CN1692117A/zh active Pending
- 2003-10-14 ES ES03770770T patent/ES2282689T3/es not_active Expired - Lifetime
- 2003-10-14 WO PCT/US2003/032698 patent/WO2004037826A2/en not_active Ceased
- 2003-10-14 AU AU2003279287A patent/AU2003279287B2/en not_active Ceased
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0268710A1 (en) * | 1986-11-25 | 1988-06-01 | Council of Scientific and Industrial Research | Improved process for the preparation of codeine from morphine |
Non-Patent Citations (1)
| Title |
|---|
| *Ikonomovski, K. Acta Pharm. Jugoslav. (1973) 23: 169-171 * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2004037826A3 (en) | 2004-07-01 |
| WO2004037826A2 (en) | 2004-05-06 |
| AU2003279287A1 (en) | 2004-05-13 |
| DE60312543T2 (de) | 2007-11-15 |
| US6579985B1 (en) | 2003-06-17 |
| EP1560833A2 (en) | 2005-08-10 |
| ES2282689T3 (es) | 2007-10-16 |
| CA2502935A1 (en) | 2004-05-06 |
| CN1692117A (zh) | 2005-11-02 |
| ATE356819T1 (de) | 2007-04-15 |
| DE60312543D1 (de) | 2007-04-26 |
| JP2006505588A (ja) | 2006-02-16 |
| MXPA05004162A (es) | 2005-06-22 |
| EP1560833B1 (en) | 2007-03-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2003279287B2 (en) | Preparation of codeine from morphine | |
| EP0140367A2 (en) | Improved process for making 6-desoxy-6-methylenenaloxone and 6-desoxy-6-methylenenaltrexone | |
| JP3049602B2 (ja) | 触媒として塩基処理されたゼオライトを使用するトリエチレンジアミンの合成 | |
| EP0208948B1 (en) | A method for optical resolution of phenylacetic acid derivative | |
| RS54523B1 (sr) | Postupak za pripremu estara (5-fluoro-2-metil-3-hinolin-2-ilmetil-indol-1-il)-sirćetne kiseline | |
| EP0055924B1 (en) | Improved process for the selective preparation of p-aminophenol from nitrobenzene | |
| KR100687167B1 (ko) | α-(2-4-디술포페닐)-Ｎ-ｔｅｒｔ-부틸니트론 및 제약상허용되는 그의 염의 신규 제조 방법 | |
| JPH09506904A (ja) | プロポフォルの精製 | |
| US20040254385A1 (en) | Process for the preparation of citalopram hydrobromide | |
| JPH02213427A (ja) | 塩基性に反応する水溶液から銅を分離する方法 | |
| JP3528699B2 (ja) | ヘキサヒドロ−２−オキソ−１Ｈ−チエノ［３，４−ｄ］イミダゾール−４−ペンタン酸の製造方法 | |
| US6774230B2 (en) | Methods for the preparation of mirtazapine intermediates | |
| JPH0436157B2 (enExample) | ||
| JP4085199B2 (ja) | Ｏ，Ｏ−ジメチル−Ｏ−（ｐ−シアノフェニル）ホスホロチオエートの製造方法 | |
| KR0177151B1 (ko) | 페닐 프로피온산 유도체의 제조방법 | |
| US8759581B2 (en) | Method of preparing 1-chloroacetamido-1,3,3,5,5-pentamethylcyclohexane | |
| PL200527B1 (pl) | Sposób otrzymywania 9-deoksy-9(Z)-hydroksyiminoerytromycyny A | |
| JP3539153B2 (ja) | シトシンの製造法 | |
| JPS6332061B2 (enExample) | ||
| JP2002513413A (ja) | ラクトースの異性化によるラクツロースシロップを製造する方法 | |
| JPS62178580A (ja) | ２，３−ジヒドロ−２，２−ジメチル−７−ヒドロキシベンゾフランの製造法 | |
| AU2002247130A1 (en) | Method for the preparation of mirtazapine intermediates | |
| JP2001206880A (ja) | ハロゲノアリルフルフリルアルコール類の製造方法 | |
| Plaut | EXTENSION OF THE SUBSTITUTED AMIDE SYNTHESIS: THE SYNTHESIS OF N-ALKYL-(ALPHA, BETA)-UNSATURATED ACID AMIDES | |
| JPH0597781A (ja) | アルキルアミノフエノールの製造法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGA | Letters patent sealed or granted (standard patent) | ||
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |