TWI260982B - Methods for preparing O-desmethylvenlafaxine - Google Patents
Methods for preparing O-desmethylvenlafaxine Download PDFInfo
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- TWI260982B TWI260982B TW091134427A TW91134427A TWI260982B TW I260982 B TWI260982 B TW I260982B TW 091134427 A TW091134427 A TW 091134427A TW 91134427 A TW91134427 A TW 91134427A TW I260982 B TWI260982 B TW I260982B
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- 238000000034 method Methods 0.000 title claims abstract description 29
- KYYIDSXMWOZKMP-UHFFFAOYSA-N O-desmethylvenlafaxine Chemical compound C1CCCCC1(O)C(CN(C)C)C1=CC=C(O)C=C1 KYYIDSXMWOZKMP-UHFFFAOYSA-N 0.000 title abstract 3
- -1 arene thiolate anion Chemical class 0.000 claims abstract description 10
- 239000002904 solvent Substances 0.000 claims abstract description 6
- 239000000203 mixture Substances 0.000 claims abstract description 5
- 238000004519 manufacturing process Methods 0.000 claims abstract description 4
- 230000001335 demethylating effect Effects 0.000 claims abstract 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 230000017858 demethylation Effects 0.000 claims description 4
- 238000010520 demethylation reaction Methods 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 3
- 239000011541 reaction mixture Substances 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims 6
- 150000001450 anions Chemical class 0.000 claims 3
- 238000006243 chemical reaction Methods 0.000 claims 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 claims 2
- 239000002202 Polyethylene glycol Substances 0.000 claims 2
- 150000004703 alkoxides Chemical class 0.000 claims 2
- ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical group CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 claims 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 claims 1
- RMVRSNDYEFQCLF-UHFFFAOYSA-M benzenethiolate Chemical compound [S-]C1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-M 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 claims 1
- 150000007944 thiolates Chemical class 0.000 claims 1
- ZIBGPFATKBEMQZ-UHFFFAOYSA-N triethylene glycol Chemical compound OCCOCCOCCO ZIBGPFATKBEMQZ-UHFFFAOYSA-N 0.000 claims 1
- 150000001335 aliphatic alkanes Chemical class 0.000 abstract 1
- 125000003710 aryl alkyl group Chemical group 0.000 abstract 1
- PNVNVHUZROJLTJ-UHFFFAOYSA-N venlafaxine Chemical compound C1=CC(OC)=CC=C1C(CN(C)C)C1(O)CCCCC1 PNVNVHUZROJLTJ-UHFFFAOYSA-N 0.000 abstract 1
- 229960004688 venlafaxine Drugs 0.000 abstract 1
- 229960004592 isopropanol Drugs 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000000967 suction filtration Methods 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
- WNAHIZMDSQCWRP-UHFFFAOYSA-N dodecane-1-thiol Chemical compound CCCCCCCCCCCCS WNAHIZMDSQCWRP-UHFFFAOYSA-N 0.000 description 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 2
- YLWCNZQVNYRELK-UHFFFAOYSA-N dodecane-1-thiol;sodium Chemical compound [Na].CCCCCCCCCCCCS YLWCNZQVNYRELK-UHFFFAOYSA-N 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- RZWQDAUIUBVCDD-UHFFFAOYSA-M sodium;benzenethiolate Chemical compound [Na+].[S-]C1=CC=CC=C1 RZWQDAUIUBVCDD-UHFFFAOYSA-M 0.000 description 1
- XRZRPHKMCVBSLA-UHFFFAOYSA-M sodium;dodecane-1-thiolate Chemical compound [Na+].CCCCCCCCCCCC[S-] XRZRPHKMCVBSLA-UHFFFAOYSA-M 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/08—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions not involving the formation of amino groups, hydroxy groups or etherified or esterified hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/10—Separation; Purification; Stabilisation; Use of additives
-
- 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)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pain & Pain Management (AREA)
- Neurology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
1260982 玫、發明說明 (發明說明應敘明：發明所屬之技術領域、先前技術、內容、實施方式及圖式簡單說明） (一） 發明所屬之技術領域 本發明係關於0 -去甲基賓拉法奇新之製法。 (二） 先前技術 〇-去甲基賓拉法奇新是賓拉法奇新之一種主要代謝物， 製作0 -去甲基賓拉法奇新之方法被描述於U . S .專利案 4，5 3 5，1 8 6號中，此方法係使用苄基阻斷基而造成相對性 地低生產量。 製作0-去甲基賓拉法奇新之步驟亦被描述於W0 00/59851 號中，其中賓拉法奇新能夠與二苯基磷化物在THF中反應 (一般經由在0°C以下加入THF中之正丁鋰至THF中之二苯 基膦來生產）而在隔夜時間中回流，其所報告之產量爲 7 3 . 8%。此外，此方法所涉及之提取步驟與大量溶劑有關。 本發明則提供在時間上及材料上皆爲有效率之0 -去甲基 賓拉法奇新之製法。 (三） 發明內容 依據本發明所提供之〇 -去甲基賓拉法奇新之製法’其包 含如描述於圖解I中式I化合物之去甲基步驟以提供式11 化合物。 -5- 1260982 酒精性介質亦可幫助產物之結晶作用。 較佳之醇類包含1至6個碳原子之直鏈或分支鏈烷基， 如甲醇、乙醇、異丙醇、丁醇等，及其混合物。在本發明 之一些較佳具體實施例中，此醇類爲異丙醇。 本發明之產量大於約75%，且一般約由85%至大於90%。 (四）實施方式 下列實例是爲了說明，而無意限制本發明於此。 實例1 將十二烷硫醇（1 2 2克）、賓拉法奇新（1 1 1克）及甲醇 鈉之甲醇性溶液（30%，90克）及PEG 400加熱至190 °C， 將甲醇蒸餾出來並在190°C下將溶液攪拌2小時，然後將溫 度降低，加入2 -丙醇（4 5 0克）’然後以水溶液HC1將pH 値調整至9 . 5 ’以吸濾法收集沉澱物’並以2 -丙醇、甲苯 、2 -丙醇和水淸洗沉積物，濕的0 -去甲基賓拉法奇新在真 空中乾燥。 產量爲87克。 iH-NMR: (Gemini 200，Varian，2 00 MHz) (DMS〇-d6) δ = 9.11 ( s，b r , 1H ; OH) , 6.98 ( d , b r , J 二 8 . 4，2H ; a rom ·)， 6.65 (d，br，J = 8.4，2H; arom.)，5.32 (s，br, 1H; OH)， 3.00 (dd， J = 12.3 及 8.5， 1H)， 2.73 (dd, J = 8.5 及 6.3, lH)，2.36(dd，J=12.3and6.3， lH)，2.15(s,6H， 2 x Me), 1.7-0.8 (m, 10H, c-hex) 實例2
將賓拉法奇新（5 · 6克）及苯硫醇鈉鹽（6 · 9克）注入PEG -8- 1260982 4 0 0 ( 2 5克）中，將反應混合物加熱至1 6 〇 °C作用5小時， 然後將溫度降低並加入水（60克），以Η3Ρ04將pH値調整 至3 . 5。以庚烷（2 5克）提取而將有機產物移除，然後以 水溶液氨將水溶液層之pH値調整至9 . 5。以吸濾法收集沉 澱物，在水中（1 0 0克）再次使其成爲泥漿狀，以吸濾法 分離並在真空中乾燥。 產量爲1克。
'NMR : (Gemini 200，Varian，200 MHz) (DM SO-d6) δ 二 9. 11 (s，br，1H ; OH), 6.98 (d，br,J = 8.4, 2 H ; a r o m . ) , 6.65 (d，b r , J =8.4, 2H ; a r om . ) , 5.32 ( s , b r , 1 H ; OH ) , 3 . 00 (dd，J = 12.3 及 8·5, 1H)，2.73 (dd，J 二 8·5 及 6.3，1H)， 2.36 (dd，J = 12.3 及 6.3, 1H)，2.15 (s, 6H，2 xMe)， 1.7-0.8 (m， 1〇H, c-hex) 實例3
將十二烷硫醇（6 9克）、賓拉法奇新（5 5克）及甲醇鈉 之甲醇性溶液（2 1 %，8 2克）注入壓力瓶中，將溫度提昇 至1 50°C並將此反應混合物攪拌2天，然後將溫度降低並過 濾此溶液，濾液以水溶液氯化氫調整pH値至9 . 5，以吸濾 法收集晶體，沉澱物以乙醇淸洗並在真空中乾燥。 產量爲42克。 ]H-NMR: (Gemini 200, Varian, 200 MHz) (DMS0-d6) δ -9 · 1 1 (s，br，1 Η ; OH) , 6 · 98 ( d，br，J = 8 · 4，2H; arom .)， 6·65 (d，br，J 二 8.4，2H ; a r o m . ) , 5.32 ( s , b r , 1 H ; OH ), 3·00 (dd， J 二 12.3 及 8.5， 1H)， 2.73 (dd， J = 8.5 及 -9- 1260982 6.3，lH)，2,36(dd,J=l2.3&6.3，lH)，2.15(s，6H， 2 x Me) , 1 .7-0.8(m, l〇H, c^hex) 實例4 步驟a十二烷硫醇鈉試劑之形成
將十二烷硫醇（2 4 6克）及在甲醇中之甲醇鈉（3 0 %，2 1 6 克）注入旋轉的蒸發器中’應用真空並使用水浴温度至 9 0 t來抽取溶劑，在接下來之步驟中使用剩下之十二烷硫 醇鈉（27 2 )而不需進一步純化。 步驟b去甲基化 將十二烷硫醇鈉（2 7 2克）、賓拉法奇新（2 5 6克）及PEG 400 ( 1 85克）之混合物在190°C下攪拌3小時，然後將溫 度降低並加入2 -丙醇（9 1 5克），以以水溶液HC 1將pH値 調整至9 · 5。以吸濾法收集沉澱物，以2 -丙醇及水淸洗此 沉澱物，將濕的〇 -去甲基賓拉法奇新在真空中乾燥。 產量爲200克。
l-NMR: (Gemini 20 0，Varian，200 MHz) (DMS〇-d6) δ二 9.11 (s，br，1H; OH) , 6.98 ( d , br , J = 8.4，2H ; arom·)， 6 . 65 ( d , br, J = 8.4，2H ; arom. ) , 5.32 ( s , br , 1H ; OH), 3.00 (dd， J 二 12.3 及 8.5， 1H)， 2.73 (dd， J = 8.5 及 6.3, 1H)，2.36 (dd，J = 12.3 及 6.3，1H)，2.15 (s，6H， 2 x Me) , 1.7-0.8 (m, 10H, c-hex) - 1 0-
Claims (1)
- 似吏冬) J Ι26ί)982 ϊ /.η.,·-.· ί — »*如屬*··*·*11· _*·_·** 拾、申請專利範圍 第91134427號「0-去甲基賓拉法奇新之製法」專利案 (2006年6月修正） 1 . 一種0-去甲基賓拉法奇新之製法，其包含以高分子量之 院類或芳煙硫醇化物陰離子，在羥基或醚性溶劑或其混 合物中將賓拉法奇新去甲基化，其中硫醇化物陰離子爲 具有8至2 0個碳原子之直鏈或分支鏈烷硫醇化物陰離子 2 .如申請專利範圍第1項之製法，其在醇、乙二醇、乙二 醇之醚類或其混合物中進行。 3 .如申請專利範圍第1項之製法，其中溶劑爲乙二醇單乙 基醚、三乙二醇、二甲基醚或聚乙二醇。 4 .如申師專利範圍第1項之製法，其中溶劑爲聚乙二醇4〇〇 〇 5. 如申請專利範圍第丨項之製法，其中反應在約丨”^至約 2 2 0 °C下進行。 6. 如申請專利範圍第5項之製法，其中此反應在約丨川^至 約2 2 0 °C下進行。 7 .如申請專利範圍第6項之製法，其中此反應在約ί 8〇。匸至 約2 0 0 °C下進行。 8 .如申請專利範圍第丨項之製法，其中進行此反應約2至 約5小時。 9 .如申把專利範圍第丨項中之製法，其中烷硫醇化物陰離 子爲十一院硫醇離子。 1260982 1 ο.如申請專利範圍第1項之製法，其中芳烴硫醇化物陰離 子具有6至1 0個碳原子。 Π .如申請專利範圍第1 0項之製法，其中芳烴硫醇化物陰離 子爲苯硫醇化物。 1 2 .如申請專利範圍第1項之製法，其中硫醇化物陰離子係 在烷氧化物存在下所產生。 1 3 .如申請專利範圍第1 2項之製法，其中烷氧化物爲甲氧化 物。 1 4 ·如申請專利範圍第1項之製法，其在硫醇化物：賓拉法奇 新多至約3 . 0 : 1之化學計量上過剩下進行。 1 5 ·如申請專利範圍第1 4項之製法，其中硫醇化物：賓拉法 奇新之莫耳比率約1 . 1 5 : 1至約2 . 5 : 1。 1 6 .如申請專利範圍第1項之製法，其進一步包含在含有i 至6個碳原子之直鏈或分支鏈烷基之醇存在下中和產物 至等電位點。 1 7 .如申請專利範圍第1 6項之製法，其中該醇爲異丙醇。 1 8 ·如申請專利範圍第丨6項之製法，其中在加入醇前將反應 混合物冷卻至約6 5 °C至約7 5 °C間。 1 9 ·如申請專利範圍第1 6項之製法，其中等電位點約p H 9 . 5 至約ρ Η 1 〇。 20·—種（Κ去甲基賓拉法奇新之製法，其包含在約18〇。(：至 約2 0 0 C下約2至約5小時，在甲醇中之甲醇鈉存在下以 十二基硫醇化物及聚乙二醇400將賓拉法奇新去甲基化 •，並在異丙醇存在下中和產物至約ρΗ9 . 5。 -2-
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US33495301P | 2001-12-04 | 2001-12-04 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW200301102A TW200301102A (en) | 2003-07-01 |
| TWI260982B true TWI260982B (en) | 2006-09-01 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW091134427A TWI260982B (en) | 2001-12-04 | 2002-11-27 | Methods for preparing O-desmethylvenlafaxine |
Country Status (28)
| Country | Link |
|---|---|
| US (4) | US6689912B2 (zh) |
| EP (1) | EP1451143B9 (zh) |
| JP (1) | JP4342312B2 (zh) |
| KR (1) | KR100939650B1 (zh) |
| CN (1) | CN1319934C (zh) |
| AR (1) | AR037622A1 (zh) |
| AT (1) | ATE403641T1 (zh) |
| AU (1) | AU2002357049B2 (zh) |
| BR (1) | BR0214701A (zh) |
| CA (1) | CA2466779C (zh) |
| CO (1) | CO5580816A2 (zh) |
| DE (1) | DE60228118D1 (zh) |
| DK (1) | DK1451143T3 (zh) |
| EC (1) | ECSP045135A (zh) |
| ES (1) | ES2311647T4 (zh) |
| HU (1) | HUP0402269A3 (zh) |
| IL (3) | IL162253A0 (zh) |
| MX (1) | MXPA04005309A (zh) |
| NO (1) | NO20042680L (zh) |
| NZ (1) | NZ533316A (zh) |
| PL (1) | PL369299A1 (zh) |
| PT (1) | PT1451143E (zh) |
| RU (1) | RU2317286C2 (zh) |
| SI (1) | SI1451143T1 (zh) |
| TW (1) | TWI260982B (zh) |
| UA (1) | UA80543C2 (zh) |
| WO (1) | WO2003048104A1 (zh) |
| ZA (1) | ZA200405250B (zh) |
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| US6342533B1 (en) | 1998-12-01 | 2002-01-29 | Sepracor, Inc. | Derivatives of (−)-venlafaxine and methods of preparing and using the same |
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| MX2008000249A (es) * | 2005-07-06 | 2008-03-18 | Sepracor Inc | Combinaciones de eszopiclona y o-desmetilvenlafaxina y metodos de tratamiento de menopausia y trastornos del estado de animo, ansiedad y cognitivos. |
| AU2006322057A1 (en) * | 2005-12-05 | 2007-06-14 | Wyeth | Process for selective synthesis of enantiomers of substituted 1-(2-amino-1-phenyl-ethyl)-cyclohexanols |
| EP1973866A1 (en) | 2005-12-20 | 2008-10-01 | Synthon B.V. | Process for making desvenlafaxine |
| JP2008546718A (ja) * | 2006-04-17 | 2008-12-25 | 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 | 実質的に純粋なｏ−デスメチルベンラファキシン及びその調製方法。 |
| MX2007016179A (es) | 2006-04-17 | 2008-03-11 | Teva Pharma | Formas cristalinas de o-desmetilvenlafaxina. |
| WO2008035369A2 (en) * | 2006-06-30 | 2008-03-27 | Alembic Limited | Novel form of o-desmethyl venlafaxine |
| CA2656167A1 (en) | 2006-07-26 | 2008-01-31 | Teva Pharmaceutical Industries Ltd. | Processes for the synthesis of o-desmethylvenlafaxine |
| US20090069601A1 (en) * | 2006-07-26 | 2009-03-12 | Valerie Niddam-Hildesheim | Processes for the synthesis of O-desmethylvenlafaxine |
| JP2008546850A (ja) * | 2006-07-26 | 2008-12-25 | 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 |
| US20080221356A1 (en) * | 2006-07-26 | 2008-09-11 | Valerie Niddam-Hildesheim | Processes for the synthesis of O-desmethylvenlafaxine |
| CA2656285A1 (en) * | 2006-07-26 | 2008-01-31 | Teva Pharmaceutical Industries Ltd. | Processes for the synthesis of o-desmethylvenlafaxine |
| US20090137846A1 (en) * | 2006-07-26 | 2009-05-28 | Valerie Niddam-Hildesheim | Processes for the synthesis of O-Desmethylvenlafaxine |
| CA2656166A1 (en) * | 2006-07-26 | 2008-01-31 | Teva Pharmaceutical Industries Ltd. | Processes for the synthesis of o-desmethylvenlafaxine |
| ES2334765B1 (es) * | 2006-08-04 | 2010-12-20 | Medichem, S.A. | Proceso mejorado para sintetizar la base libre de la desvenlafaxina ysales o solvatos de la misma. |
| AU2008211711A1 (en) * | 2007-01-31 | 2008-08-07 | Generics [Uk] Limited | Process for the preparation of O-desmethyl venlafaxine |
| WO2008112313A2 (en) * | 2007-03-14 | 2008-09-18 | Teva Pharmaceutical Industries Ltd. | Processes for preparing solid states of o-desmethylvenlafaxine succinate |
| CA2692738A1 (en) * | 2007-07-12 | 2009-01-15 | Dr. Reddy's Laboratories, Ltd. | O-desmethylvenlafaxine |
| WO2009010990A2 (en) * | 2007-07-16 | 2009-01-22 | Matrix Laboratories Limited | Process for the preparation of o-desmethylvenlafaxine succinate polymorphic forms |
| WO2009034434A2 (en) * | 2007-09-10 | 2009-03-19 | Cadila Pharmaceuticals Limited | An improved process for the preparation of o-desmethylvenlafaxine |
| CA2703647A1 (en) | 2007-10-26 | 2009-04-30 | Generics [Uk] Limited | Process for preparing o-desmethylvenlafaxine |
| US8063250B2 (en) * | 2007-11-26 | 2011-11-22 | Teva Pharmaceutical Industries, Ltd. | Crystal forms of O-desmethylvenlafaxine fumarate |
| WO2009084038A2 (en) * | 2007-12-28 | 2009-07-09 | Ind-Swift Laboratories Limited | Improved process for the preparation of 0-desmethyl-venlafaxine |
| WO2009151494A1 (en) * | 2008-03-06 | 2009-12-17 | Teva Pharmaceutical Industries Ltd. | Processes for the preparation of o-desmethylvenlafaxine, free from its dimer impurities |
| EP2119695A1 (en) | 2008-05-16 | 2009-11-18 | Krka | Preparation of O-desmethylvenlafaxine salts |
| EP2119696A1 (en) | 2008-05-16 | 2009-11-18 | Krka | Preparation of O-desmethylvenlafaxine salts |
| EP2297087A2 (en) * | 2008-06-16 | 2011-03-23 | Teva Pharmaceutical Industries Ltd. | Solid states of o-desmethylvenlaf axine salts |
| US20100016638A1 (en) * | 2008-07-21 | 2010-01-21 | Zdenko Hamersak | Method for preparation of o-desmethylvenlafaxine using polythiolates |
| US20110263718A1 (en) * | 2008-07-30 | 2011-10-27 | Generics [Uk] Limited | Process for the preparation of o-desmethylvenlafaxine |
| CZ2008756A3 (cs) | 2008-11-27 | 2010-03-24 | Zentiva, A. S. | Zpusob prípravy desvenlafaxinu a jeho solí |
| CZ200969A3 (cs) | 2009-02-06 | 2010-06-30 | Zentiva, K.S. | Nové soli desvenlafaxinu a zpusob jejich prípravy |
| CZ2009454A3 (cs) | 2009-07-15 | 2010-11-10 | Zentiva, K. S. | Zpusob prípravy desvenlafaxinu a jeho solí |
| AU2010272377A1 (en) | 2009-07-16 | 2012-01-19 | Cipla Limited | Process for the preparation of O-desmethyl venlafaxine and intermediate for use therein |
| US20110098506A1 (en) * | 2009-10-26 | 2011-04-28 | Intas Pharmaceuticals Limited | Method of preparing o-desmethylvenlafaxine |
| US20110184067A1 (en) * | 2010-01-25 | 2011-07-28 | Intas Pharmaceuticals Ltd. | O-desmethylvenlafaxine succinate polymorph & process for preparing thereof |
| CA2795023A1 (en) | 2010-03-29 | 2011-10-06 | Pliva Hrvatska D.O.O. | Crystal forms of o-desmethylvenlafaxine fumarate |
| CZ303249B6 (cs) | 2010-04-06 | 2012-06-20 | Zentiva, K.S. | Zpusob výroby 4-(2-(substituovaných)-1-(1-hydroxycyklohexyl)ethyl)fenolu O-demethylací jejich methyletheru pomocí nepáchnoucích aromatických thiolu |
| EP2394976A1 (en) | 2010-06-11 | 2011-12-14 | LEK Pharmaceuticals d.d. | Process for demethylating aromatic methyl ethers using 3-mercaptopropionic acid |
| WO2018146529A1 (en) | 2017-02-09 | 2018-08-16 | R L Finechem Private Limited | A process for preparation of1-[2-(dimethylamino)-1-(4-hydroxyphenyl) ethyl]-cyclohexanol and salts thereof |
| CN109232189B (zh) * | 2018-09-25 | 2021-10-08 | 杭州盛弗泰新材料科技有限公司 | 一种高纯度1-羟基芘的制备方法 |
| CN109665966A (zh) * | 2018-11-01 | 2019-04-23 | 山东蒲济医药科技有限公司 | 一种琥珀酸去甲文拉法辛化合物的制备方法 |
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| DE2741009A1 (de) * | 1976-09-22 | 1978-03-23 | Sandoz Ag | 4-styryl-4-indolinol-derivate, ihre verwendung und herstellung |
| US4535186A (en) | 1983-04-19 | 1985-08-13 | American Home Products Corporation | 2-Phenyl-2-(1-hydroxycycloalkyl or 1-hydroxycycloalk-2-enyl)ethylamine derivatives |
| CA1227304A (en) | 1984-08-01 | 1987-09-29 | Raymond C. Francis | Delignification of pulp |
| 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 |
| US6342533B1 (en) * | 1998-12-01 | 2002-01-29 | Sepracor, Inc. | Derivatives of (−)-venlafaxine and methods of preparing and using the same |
| CZ20013607A3 (cs) | 1999-04-06 | 2002-06-12 | Sepracor Inc. | Farmaceutický prostředek |
| AU5738700A (en) | 1999-06-15 | 2001-01-02 | American Home Products Corporation | Enantiomers of o-desmethyl venlafaxine |
| WO2002006453A2 (en) | 2000-07-18 | 2002-01-24 | Bayer Aktiengesellschaft | Regulation of human desc1-like serine protease |
| HN2002000030A (es) * | 2001-02-12 | 2004-06-07 | Wyeth Corp | Nueva sal succinato de o-desmetil-venlafaxina |
| UA80543C2 (en) * | 2001-12-04 | 2007-10-10 | Wyeth Corp | Method for the preparation of o-desmethylvenlafaxine |
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