CN101591247A - 合成4-(4-甲酯基苯基)丁醛的方法 - Google Patents
合成4-(4-甲酯基苯基)丁醛的方法 Download PDFInfo
- Publication number
- CN101591247A CN101591247A CNA2008100383751A CN200810038375A CN101591247A CN 101591247 A CN101591247 A CN 101591247A CN A2008100383751 A CNA2008100383751 A CN A2008100383751A CN 200810038375 A CN200810038375 A CN 200810038375A CN 101591247 A CN101591247 A CN 101591247A
- Authority
- CN
- China
- Prior art keywords
- organic solvent
- butyraldehyde
- methoxycarbonyl phenyl
- alcohol
- obtains
- 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
Links
- 238000000034 method Methods 0.000 title claims abstract description 22
- PKKOQVAJFXOJOA-UHFFFAOYSA-N methyl 4-(4-oxobutyl)benzoate Chemical compound COC(=O)C1=CC=C(CCCC=O)C=C1 PKKOQVAJFXOJOA-UHFFFAOYSA-N 0.000 title claims abstract description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 19
- -1 parabromobenzoic acid methyl esters Chemical class 0.000 claims abstract description 16
- 239000003960 organic solvent Substances 0.000 claims abstract description 15
- 238000006243 chemical reaction Methods 0.000 claims abstract description 12
- 238000009833 condensation Methods 0.000 claims abstract description 7
- 230000005494 condensation Effects 0.000 claims abstract description 7
- 239000000377 silicon dioxide Substances 0.000 claims abstract description 6
- 238000000638 solvent extraction Methods 0.000 claims abstract description 5
- 238000009835 boiling Methods 0.000 claims abstract description 3
- 239000000243 solution Substances 0.000 claims description 26
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 24
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 8
- 238000000605 extraction Methods 0.000 claims description 8
- 238000005406 washing Methods 0.000 claims description 8
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 7
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 6
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 4
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 3
- 239000012046 mixed solvent Substances 0.000 claims description 2
- 239000012074 organic phase Substances 0.000 claims description 2
- 239000012071 phase Substances 0.000 claims description 2
- 239000012047 saturated solution Substances 0.000 claims description 2
- 238000010189 synthetic method Methods 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims 2
- 239000007795 chemical reaction product Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- NYDXNILOWQXUOF-UHFFFAOYSA-L disodium;2-[[4-[2-(2-amino-4-oxo-1,7-dihydropyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]amino]pentanedioate Chemical compound [Na+].[Na+].C=1NC=2NC(N)=NC(=O)C=2C=1CCC1=CC=C(C(=O)NC(CCC([O-])=O)C([O-])=O)C=C1 NYDXNILOWQXUOF-UHFFFAOYSA-L 0.000 abstract description 3
- 229960003349 pemetrexed disodium Drugs 0.000 abstract description 3
- 239000003795 chemical substances by application Substances 0.000 abstract description 2
- 230000002194 synthesizing effect Effects 0.000 abstract description 2
- IVIRGDUYMLTXHH-UHFFFAOYSA-N methyl 4-(1-oxobutan-2-yl)benzoate Chemical compound C(=O)(OC)C1=CC=C(C=C1)C(C=O)CC IVIRGDUYMLTXHH-UHFFFAOYSA-N 0.000 abstract 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 16
- 239000012044 organic layer Substances 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 8
- 230000036571 hydration Effects 0.000 description 8
- 238000006703 hydration reaction Methods 0.000 description 8
- XIXADJRWDQXREU-UHFFFAOYSA-M lithium acetate Chemical class [Li+].CC([O-])=O XIXADJRWDQXREU-UHFFFAOYSA-M 0.000 description 8
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- 239000000047 product Substances 0.000 description 6
- 238000002156 mixing Methods 0.000 description 5
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000010025 steaming Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
本发明提供了一致合成4－(4－甲酯基苯基)丁醛的方法，包括如下步骤：将对溴苯甲酸甲酯和3－丁烯－1－醇进行缩合，后处理时采用有机溶剂萃取，加入硅胶脱色，蒸去有机溶剂后即可得到4－(4－甲酯基苯基)丁醛。用本发明方法得到的产品收率可达80％以上，GC检测纯度可达95％以上，可以不需精制直接用于合成培美曲塞二钠的下一步溴代反应。本发明方法工艺操作简单，所用试剂价廉且来源易得，适合工业化生产。
Description
技术领域
本发明涉及合成4-(4-甲酯基苯基)丁醛的方法。
背景技术
4-(4-甲酯基苯基)丁醛是合成抗肿瘤药培美曲塞二钠的关键中间体。关于其合成方法报道的主要有三种：一是J.Org.Chem.，1990，55：3222-7报道采用3-丁炔-1-醇与对溴苯甲酸甲酯缩合，然后再经钯炭氢化还原，PCC氧化醇得到产品，此法步骤繁琐，且试剂昂贵；二是Tetrahedron Letters，1989，30：6629-32报道采用3-丁烯-1-醇与对溴苯甲酸甲酯缩合，经柱层析分离得到纯品，此法需要柱层析，不适合工业化生产；三是化工时刊，2006，20：54-55.报道将3-丁烯-1-醇与对溴苯甲酸甲酯缩合得到的4-(4-甲酯基苯基)丁醛粗品与亚硫酸氢钠反应形成磺酸盐，再用盐酸处理得到纯品，此法得到的产品纯度高，但总收率只有38％。
发明内容
本发明的目的是提供一种合成4-(4-甲酯基苯基)丁醛的方法，以克服上述技术的不足，以便于工业化生产。
本发明的方法包括如下步骤：
将对溴苯甲酸甲酯和3-丁烯-1-醇进行缩合，然后采用有机溶剂萃取，萃取相加入硅胶脱色，蒸去有机溶剂后即可得到4-(4-甲酯基苯基)丁醛；
具体的包括如下步骤：
(1)将对溴苯甲酸甲酯溶于DMF中，加入二水合乙酸锂，氯化锂，四丁基溴化铵，鼓氮气，再加入3-丁烯-1-醇，乙酸钯进行缩合反应，然后加入水终止反应；再加入有机溶剂萃取，将得到的有机相，用碳酸氢钠溶液调pH至7～8后再用水洗，然后硅胶脱色，减压蒸去溶剂得到产品；
显然，上述过程中，采用其他碱性物质，如碳酸钠、氢氧化钠或氢氧化钾等，或者直接用水洗涤至7～8后，再硅胶脱色，也能够实现本发明的目的。
所说的有机溶剂选自C5-C8的烷烃、石油醚或C2-C4的醚中的一种或一种以上；
所说的C5-C8的烷烃优选正己烷或环己烷，C2-C4的醚优选异丙醚；
优选正己烷(或环己烷)和乙酸乙酯的混合溶剂，混合的体积比例为：4～8∶1。
所说的碳酸氢钠溶液的重量浓度为1％～饱和溶液，优选饱和碳酸氢钠溶液；
优选的，缩合物的水溶液与有机溶剂的体积比为1∶0.1～1，优选0.15～0.50；
用本发明方法得到的产品收率可达80％以上，GC检测纯度可达95％以上，可以不需精制直接用于合成培美曲塞二钠的下一步溴代反应。本发明方法工艺操作简单，所用试剂价廉且来源易得，适合工业化生产。
具体实施方式
下面结合实施例对本发明作进一步详细的说明。
实施例1
将对溴苯甲酸甲酯(85.0g，0.395mol)溶于1L DMF中，加入二水合乙酸锂45.0g，氯化锂50.0g，四丁基溴化铵60.0g，鼓氮气5分钟，再加入3-丁烯-1-醇(34.0g，0.472mol)，乙酸钯2.3g，于60℃下搅拌反应10小时。冷却至25℃，加水1L，用环己烷和乙酸乙酯(6∶1，体积比)混合溶液300ml萃取3次，合并有机层，有机层用饱和碳酸氢钠溶液调pH至8后，再用水(4×500ml)洗涤。加硅胶80g搅拌半小时脱色，所得淡黄色溶液40℃减压蒸干得4-(4-甲酯基苯基)丁醛70.0g，收率86.0％，GC检测纯度为96.3％。
实施例2
将对溴苯甲酸甲酯(10.8g，0.050mol)溶于150ml DMF中，加入二水合乙酸锂5.7g，氯化锂6.4g，四丁基溴化铵7.6g，鼓氮气5分钟，再加入3-丁烯-1-醇(4.3g，0.060mol)，乙酸钯0.3g，于60℃下搅拌反应10小时。冷却至25℃，加水200ml，用石油醚(60～90℃)和乙酸乙酯(7∶1，体积比)混合溶液100ml分3次萃取，合并有机层，有机层用饱和碳酸氢钠溶液调pH至7后，再用水(5×50ml)洗涤。加硅胶10g搅拌半小时脱色，所得淡黄色溶液40℃减压蒸干得4-(4-甲酯基苯基)丁醛8.4g，收率81.6％，GC检测纯度为96.1％。
实施例3
将对溴苯甲酸甲酯(10.8g，0.050mol)溶于150ml DMF中，加入二水合乙酸锂5.7g，氯化锂6.4g，四丁基溴化铵7.6g，鼓氮气5分钟，再加入3-丁烯-1-醇(4.3g，0.060mol)，乙酸钯0.3g，于60℃下搅拌反应10小时。冷却至25℃，加水200ml，用异丙醚和乙酸乙酯(9∶1，体积比)混合溶液100ml分3次萃取，合并有机层，有机层用饱和碳酸氢钠溶液调pH至7.5后，再用水(5×50ml)洗涤。加硅胶10g搅拌半小时脱色，所得淡黄色溶液40℃减压蒸干得4-(4-甲酯基苯基)丁醛8.0g，收率77.7％，GC检测纯度为95.2％。
实施例4
将对溴苯甲酸甲酯(10.8g，0.050mol)溶于150ml DMF中，加入二水合乙酸锂5.7g，氯化锂6.4g，四丁基溴化铵7.6g，鼓氮气5分钟，再加入3-丁烯-1-醇(4.3g，0.060mol)，乙酸钯0.3g，于60℃下搅拌反应10小时。冷却至25℃，加水200ml，用正己烷和乙酸乙酯(4∶1，体积比)混合溶液100ml分3次萃取，合并有机层，有机层用重量浓度5％碳酸氢钠溶液调pH至7.6后，再用水(5×50ml)洗涤。加硅胶10g搅拌半小时脱色，所得淡黄色溶液40℃减压蒸干得4-(4-甲酯基苯基)丁醛8.2g，收率79.6％，GC检测纯度为95.0％。
实施例4
将对溴苯甲酸甲酯(10.8g，0.050mol)溶于150ml DMF中，加入二水合乙酸锂5.7g，氯化锂6.4g，四丁基溴化铵7.6g，鼓氮气5分钟，再加入3-丁烯-1-醇(4.3g，0.060mol)，乙酸钯0.3g，于60℃下搅拌反应10小时。冷却至25℃，加水200ml，用正己烷和乙酸乙酯(8∶1，体积比)混合溶液120ml分3次萃取，合并有机层，有机层用重量浓度2％碳酸氢钠溶液调pH至7后，再用水(5×50ml)洗涤。加硅胶10g搅拌半小时脱色，所得淡黄色溶液40℃减压蒸干得4-(4-甲酯基苯基)丁醛7.6g，收率73.8％，GC检测纯度为96.5％。
实施例5
将对溴苯甲酸甲酯(10.8g，0.050mol)溶于150ml DMF中，加入二水合乙酸锂5.7g，氯化锂6.4g，四丁基溴化铵7.6g，鼓氮气5分钟，再加入3-丁烯-1-醇(4.3g，0.060mol)，乙酸钯0.3g，于60℃下搅拌反应10小时。冷却至25℃，加水200ml，用环己烷100ml分3次萃取，合并有机层，有机层用饱和碳酸氢钠溶液调pH至7后，再用水(5×50ml)洗涤。加硅胶10g搅拌半小时脱色，所得淡黄色溶液40℃减压蒸干得4-(4-甲酯基苯基)丁醛5.4g，收率52.4％，GC检测纯度为96.8％。
实施例6
将对溴苯甲酸甲酯(10.8g，0.050mol)溶于150ml DMF中，加入二水合乙酸锂5.7g，氯化锂6.4g，四丁基溴化铵7.6g，鼓氮气5分钟，再加入3-丁烯-1-醇(4.3g，0.060mol)，乙酸钯0.3g，于60℃下搅拌反应10小时。冷却至25℃，加水200ml，用乙酸乙酯120ml分3次萃取，合并有机层，有机层用饱和碳酸氢钠溶液调pH至8后，再用水(5×50ml)洗涤。加硅胶10g搅拌半小时脱色，所得淡黄色溶液40℃减压蒸干得4-(4-甲酯基苯基)丁醛9.0g，收率87.4％，GC检测纯度为81.6％。
Claims (9)
1.一种合成4-(4-甲酯基苯基)丁醛的合成方法，其特征在于，包括如下步骤：将对溴苯甲酸甲酯和3-丁烯-1-醇进行缩合，反应产物采用有机溶剂萃取，萃取相加入硅胶脱色，蒸去有机溶剂后即可得到4-(4-甲酯基苯基)丁醛。
2.根据权利要求1所述的方法，其特征在于，所说的有机溶剂选自C5-C8的烷烃、石油醚或C2-C4的醚中的一种或一种以上。
3.根据权利要求2所述的方法，其特征在于，所说的C5-C8的烷烃选自正己烷或环己烷，C2-C4的醚选自异丙醚。
4.根据权利要求3所述的方法，其特征在于，所说的有机溶剂选自正己烷或环己烷和乙酸乙酯的混合溶剂，混合的体积比例为：4～8∶1。
5.根据权利要求1所述的方法，其特征在于，具体包括如下步骤：将对溴苯甲酸甲酯和3-丁烯-1-醇进行缩合，加入水终止反应，然后采用有机溶剂萃取，将得到的有机相，用碳酸氢钠溶液调pH至7～8后再用水洗，然后硅胶脱色，蒸去有机溶剂后，即可得到4-(4-甲酯基苯基)丁醛。
6.根据权利要求5所述的方法，其特征在于，所说的碳酸氢钠溶液的重量浓度为1％～饱和溶液。
7.根据权利要求6所述的方法，其特征在于，碳酸氢钠溶液为饱和碳酸氢钠溶液。
8.根据权利要求5～7任一项所述的方法，其特征在于，加入水后得到的混合物与有机溶剂的体积比为1∶0.1～1。
9.根据权利要求8所述的方法，其特征在于，加入水后得到的混合物与有机溶剂的体积比为1∶0.15～0.50。
Priority Applications (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810038375A CN101591247B (zh) | 2008-05-30 | 2008-05-30 | 合成4-(4-甲酯基苯基)丁醛的方法 |
| PCT/CN2008/073182 WO2009143684A1 (zh) | 2008-05-30 | 2008-11-25 | 培美曲塞二钠及其中间体4-(4-甲酯基苯基)丁醛的制备方法 |
| US12/995,257 US8507716B2 (en) | 2008-05-30 | 2008-11-25 | Process for preparing pemetrexed disodium and its intermediate, 4-(4-carbomethoxyphenyl) butanal |
| EP08874449A EP2301909A4 (en) | 2008-05-30 | 2008-11-25 | PROCESS FOR THE PREPARATION OF PEMETREXED DISODIUM AND ITS INTERMEDIATE 4- (4-CARBOMETHYXYPHENYL) BUTANAL |
| ARP090100049A AR076821A1 (es) | 2008-05-30 | 2009-01-08 | Un procedimiento para la preparacion de pemetrexed disodico y un procedimiento para la preparacion del 4- (4- carbometoxifenil) butanal |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810038375A CN101591247B (zh) | 2008-05-30 | 2008-05-30 | 合成4-(4-甲酯基苯基)丁醛的方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101591247A true CN101591247A (zh) | 2009-12-02 |
| CN101591247B CN101591247B (zh) | 2012-09-05 |
Family
ID=41376560
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200810038375A Active CN101591247B (zh) | 2008-05-30 | 2008-05-30 | 合成4-(4-甲酯基苯基)丁醛的方法 |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US8507716B2 (zh) |
| EP (1) | EP2301909A4 (zh) |
| CN (1) | CN101591247B (zh) |
| AR (1) | AR076821A1 (zh) |
| WO (1) | WO2009143684A1 (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107628947A (zh) * | 2017-09-14 | 2018-01-26 | 浙江工业大学 | 一种培美曲塞二钠关键中间体的制备方法 |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010028105A2 (en) * | 2008-09-08 | 2010-03-11 | Dr. Reddy's Laboratories Ltd. | Amorphous pemetrexed disodium |
| EP2675808A4 (en) * | 2011-02-15 | 2014-07-09 | Hetero Research Foundation | PROCESS FOR OBTAINING DISODIUM PEMETREXED |
| US9051322B2 (en) * | 2011-03-23 | 2015-06-09 | Scinopharm Taiwan, Ltd. | Process for the production of a pemetrexed salt |
| ITRM20120398A1 (it) * | 2012-08-08 | 2014-02-09 | Berlin Chemie Ag | Procedimento di sintesi pemetrexed e suo sale di lisina. |
| KR101372788B1 (ko) * | 2013-08-12 | 2014-03-10 | 제일약품주식회사 | 고순도의 페메트렉시드 이나트륨 염의 제조방법 |
| KR101578093B1 (ko) * | 2013-09-05 | 2015-12-16 | 주식회사 삼양바이오팜 | 고순도 페메트렉세드 제조를 위한 향상된 중간체 제조 방법 및 이를 사용하여 고순도 페메트렉세드를 제조하는 방법 |
| CN115093415A (zh) * | 2019-05-13 | 2022-09-23 | 南京制药厂有限公司 | 培美曲塞二钠原料药中残留金属钯的去除方法 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3210325A (en) * | 1962-10-15 | 1965-10-05 | Goodrich Co B F | Copolymers of polyesters derived from hydroxymethyl stearic acid |
| ZA987550B (en) | 1997-09-26 | 2000-02-21 | Lilly Co Eli | Processes and intermediates useful to make antifolates. |
| UA53742C2 (uk) * | 1997-09-26 | 2003-02-17 | Елі Ліллі Енд Компані | Спосіб одержання альдегідів, які використовують при синтезі сполук, цінних як антифолати |
| CN1800169B (zh) | 2004-12-30 | 2010-06-23 | 上海金色医药科技发展有限公司 | 培美曲塞二钠盐关键中间体及其合成方法，以及由该中间体合成培美曲塞二钠盐的方法 |
-
2008
- 2008-05-30 CN CN200810038375A patent/CN101591247B/zh active Active
- 2008-11-25 US US12/995,257 patent/US8507716B2/en not_active Expired - Fee Related
- 2008-11-25 EP EP08874449A patent/EP2301909A4/en not_active Withdrawn
- 2008-11-25 WO PCT/CN2008/073182 patent/WO2009143684A1/zh active Application Filing
-
2009
- 2009-01-08 AR ARP090100049A patent/AR076821A1/es unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107628947A (zh) * | 2017-09-14 | 2018-01-26 | 浙江工业大学 | 一种培美曲塞二钠关键中间体的制备方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2009143684A1 (zh) | 2009-12-03 |
| EP2301909A4 (en) | 2011-11-30 |
| AR076821A1 (es) | 2011-07-13 |
| EP2301909A1 (en) | 2011-03-30 |
| CN101591247B (zh) | 2012-09-05 |
| US8507716B2 (en) | 2013-08-13 |
| US20110124861A1 (en) | 2011-05-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101591247A (zh) | 合成4-(4-甲酯基苯基)丁醛的方法 | |
| CN101293811B (zh) | 由虫白蜡制备高级烷醇混合物的方法 | |
| CN101613341B (zh) | 一种瑞舒伐他汀钙侧链关键中间体的合成方法 | |
| CN108299296B (zh) | 一种菲啶类杂环化合物的制备方法 | |
| CN108191829B (zh) | 应用富马酸沃诺拉赞中间体ⅳ制备富马酸沃诺拉赞的方法 | |
| CN101445431B (zh) | 氟代苯酚的制备方法 | |
| CN104974073A (zh) | 一种制备西洛多辛中间体的方法 | |
| CN106748921B (zh) | 一种芳砜基二氟乙酸盐类化合物、制备方法及其应用 | |
| CN110028403A (zh) | 一种合成丁二酸类化合物的方法 | |
| Sun et al. | Visible‐Light‐Promoted Regio‐and Stereoselective Oxyalkenyl‐ation of Phosphinyl Allenes | |
| CN102863361B (zh) | 甲砜霉素的手性催化合成方法 | |
| CN103265417B (zh) | 一种4-[2-(反式-4-烷基环己基)乙基]环己酮的合成方法 | |
| CN105924360A (zh) | 一种(1r,2s)-2-(3,4-二氟苯基)环丙胺的合成方法 | |
| CN101041631B (zh) | 改进的β-胡萝卜素合成工艺 | |
| CN109776407B (zh) | 一种2-甲基-4-羟甲基喹啉及其衍生物的制备方法 | |
| CN104803978B (zh) | 一种埃索美拉唑镁的制备方法 | |
| CN103435477B (zh) | 一种合成对乙氧基苯甲酸的方法 | |
| CN105130725A (zh) | 一种制备γ-酮羰基类化合物的方法 | |
| CN104987325B (zh) | 一种伏立康唑的制备方法 | |
| CN109206396A (zh) | 2-c-甲基-4,5-o-(1-甲基乙烯基)-d-阿拉伯糖酸乙酯的制备方法 | |
| CN103044361B (zh) | 一种（2r,3s）-环氧化氨基苯丁烷的制备方法 | |
| CN105859620B (zh) | 一类6-三氯甲基菲啶类化合物及其制备方法和应用 | |
| CN106749131B (zh) | 消旋化制备雷美替胺中间体方法 | |
| CN105218595B (zh) | 一种含[2P2N]Cu(I)光敏剂的铁铁氢化酶模型物及其制备方法 | |
| CN107188786B (zh) | 一种医药中间体光学纯环戊烯醇的制备方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| ASS | Succession or assignment of patent right |
Free format text: FORMER OWNER: SHANGHAI DISAINUO CHEMICAL PHARMACEUTICAL CO., LTD. Owner name: SHANGHAI XIDI PHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: SHANGHAI DESANO PHARMACEUTICAL CO., LTD. Effective date: 20101221 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 201203 NO. 1479, ZHANGHENG ROAD, ZHANGJIANG HIGH-TECH. PARK, PUDONG NEW DISTRICT, SHANGHAI TO: 201203 BUILDING 9, NO. 1999, ZHANGHENG ROAD, ZHANGJIANG HIGH-TECH. PARK, PUDONG NEW DISTRICT, SHANGHAI |
|
| TA01 | Transfer of patent application right |
Effective date of registration: 20101221 Address after: 201203, building 1999, No. 9 Zhang Heng Road, Zhangjiang hi tech park, Shanghai, Pudong New Area Applicant after: Shanghai Xidi Pharmaceutical Co., Ltd. Address before: 201203 Zhang Heng road Shanghai, Pudong New Area Zhangjiang hi tech Park No. 1479 Applicant before: Shanghai Desano Pharmaceutical Co.,Ltd. Co-applicant before: Shanghai Disainuo Chemical Pharmaceutical Co., Ltd. |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C56 | Change in the name or address of the patentee |
Owner name: SHANGHAI CHUANGNUO PHARMACEUTICAL CO., LTD. Free format text: FORMER NAME: SHANGHAI XIDI PHARMACEUTICAL CO., LTD. |
|
| CP01 | Change in the name or title of a patent holder |
Address after: 201203, building 1999, No. 9 Zhang Heng Road, Zhangjiang hi tech park, Shanghai, Pudong New Area Patentee after: Shanghai Chuangnuo Pharmaceutical Co., Ltd. Address before: 201203, building 1999, No. 9 Zhang Heng Road, Zhangjiang hi tech park, Shanghai, Pudong New Area Patentee before: Shanghai Xidi Pharmaceutical Co., Ltd. |