CN102134208B - [r,r]-哌甲酯中间体及其类似物以及它们的合成与应用 - Google Patents
[r,r]-哌甲酯中间体及其类似物以及它们的合成与应用 Download PDFInfo
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- CN102134208B CN102134208B CN201010300811.5A CN201010300811A CN102134208B CN 102134208 B CN102134208 B CN 102134208B CN 201010300811 A CN201010300811 A CN 201010300811A CN 102134208 B CN102134208 B CN 102134208B
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- 229960001344 methylphenidate Drugs 0.000 title abstract description 18
- 238000003786 synthesis reaction Methods 0.000 title abstract description 10
- 230000015572 biosynthetic process Effects 0.000 title abstract description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 39
- 238000006243 chemical reaction Methods 0.000 claims description 48
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 25
- 238000000034 method Methods 0.000 claims description 18
- 230000004224 protection Effects 0.000 claims description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- -1 phenylacetic acid ester compound Chemical class 0.000 claims description 11
- DCERHCFNWRGHLK-UHFFFAOYSA-N C[Si](C)C Chemical compound C[Si](C)C DCERHCFNWRGHLK-UHFFFAOYSA-N 0.000 claims description 10
- 238000007363 ring formation reaction Methods 0.000 claims description 9
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 8
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- 238000007259 addition reaction Methods 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 238000010189 synthetic method Methods 0.000 claims description 7
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical class [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 claims description 6
- 125000003368 amide group Chemical group 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 230000001476 alcoholic effect Effects 0.000 claims description 3
- 239000003513 alkali Substances 0.000 claims description 3
- WLJVXDMOQOGPHL-UHFFFAOYSA-N benzyl-alpha-carboxylic acid Natural products OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 claims description 3
- 239000003153 chemical reaction reagent Substances 0.000 claims description 3
- OVEHNNQXLPJPPL-UHFFFAOYSA-N lithium;n-propan-2-ylpropan-2-amine Chemical compound [Li].CC(C)NC(C)C OVEHNNQXLPJPPL-UHFFFAOYSA-N 0.000 claims description 3
- ZFFBIQMNKOJDJE-UHFFFAOYSA-N 2-bromo-1,2-diphenylethanone Chemical compound C=1C=CC=CC=1C(Br)C(=O)C1=CC=CC=C1 ZFFBIQMNKOJDJE-UHFFFAOYSA-N 0.000 claims description 2
- AFRJJFRNGGLMDW-UHFFFAOYSA-N lithium amide Chemical compound [Li+].[NH2-] AFRJJFRNGGLMDW-UHFFFAOYSA-N 0.000 claims description 2
- 229960003424 phenylacetic acid Drugs 0.000 claims description 2
- 239000003279 phenylacetic acid Substances 0.000 claims description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 45
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- DUGOZIWVEXMGBE-UHFFFAOYSA-N Methylphenidate Chemical compound C=1C=CC=CC=1C(C(=O)OC)C1CCCCN1 DUGOZIWVEXMGBE-UHFFFAOYSA-N 0.000 description 25
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 22
- 239000000543 intermediate Substances 0.000 description 21
- 239000000047 product Substances 0.000 description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 230000003287 optical effect Effects 0.000 description 16
- 239000007787 solid Substances 0.000 description 16
- CRZQGDNQQAALAY-UHFFFAOYSA-N Methyl benzeneacetate Chemical compound COC(=O)CC1=CC=CC=C1 CRZQGDNQQAALAY-UHFFFAOYSA-N 0.000 description 14
- 0 C*c1c(*)c(*)c(C)[o]1 Chemical compound C*c1c(*)c(*)c(C)[o]1 0.000 description 13
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
- 239000000126 substance Substances 0.000 description 12
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 11
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 10
- 239000003814 drug Substances 0.000 description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 7
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical group [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 229910052736 halogen Inorganic materials 0.000 description 6
- 150000002367 halogens Chemical group 0.000 description 6
- FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 description 6
- 235000017550 sodium carbonate Nutrition 0.000 description 6
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 239000007789 gas Substances 0.000 description 5
- 239000005457 ice water Substances 0.000 description 5
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- JUMYIBMBTDDLNG-OJERSXHUSA-N hydron;methyl (2r)-2-phenyl-2-[(2r)-piperidin-2-yl]acetate;chloride Chemical compound Cl.C([C@@H]1[C@H](C(=O)OC)C=2C=CC=CC=2)CCCN1 JUMYIBMBTDDLNG-OJERSXHUSA-N 0.000 description 4
- 150000002466 imines Chemical class 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 229940099204 ritalin Drugs 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 4
- 235000002639 sodium chloride Nutrition 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 3
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- DUGOZIWVEXMGBE-CHWSQXEVSA-N dexmethylphenidate Chemical compound C([C@@H]1[C@H](C(=O)OC)C=2C=CC=CC=2)CCCN1 DUGOZIWVEXMGBE-CHWSQXEVSA-N 0.000 description 3
- 229960001042 dexmethylphenidate Drugs 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- QAZLUNIWYYOJPC-UHFFFAOYSA-M sulfenamide Chemical compound [Cl-].COC1=C(C)C=[N+]2C3=NC4=CC=C(OC)C=C4N3SCC2=C1C QAZLUNIWYYOJPC-UHFFFAOYSA-M 0.000 description 3
- 230000002194 synthesizing effect Effects 0.000 description 3
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 108090000317 Chymotrypsin Proteins 0.000 description 2
- FEWJPZIEWOKRBE-LWMBPPNESA-L D-tartrate(2-) Chemical compound [O-]C(=O)[C@@H](O)[C@H](O)C([O-])=O FEWJPZIEWOKRBE-LWMBPPNESA-L 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 150000001336 alkenes Chemical class 0.000 description 2
- 150000001414 amino alcohols Chemical class 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 229960002376 chymotrypsin Drugs 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- HGBOYTHUEUWSSQ-UHFFFAOYSA-N pentanal Chemical compound CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 2
- 150000003053 piperidines Chemical class 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000010948 rhodium Substances 0.000 description 2
- 230000000707 stereoselective effect Effects 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- JMXKSZRRTHPKDL-UHFFFAOYSA-N titanium ethoxide Chemical compound [Ti+4].CC[O-].CC[O-].CC[O-].CC[O-] JMXKSZRRTHPKDL-UHFFFAOYSA-N 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- OGSBQJBITGRKOF-UHFFFAOYSA-N C(C)(=O)OC.BrC1=CC=CC=C1 Chemical compound C(C)(=O)OC.BrC1=CC=CC=C1 OGSBQJBITGRKOF-UHFFFAOYSA-N 0.000 description 1
- WTAVBYHGJYGHET-TZMCWYRMSA-N COC(=O)[C@@H]([C@H]1CCCCN1)c1ccccc1OC Chemical compound COC(=O)[C@@H]([C@H]1CCCCN1)c1ccccc1OC WTAVBYHGJYGHET-TZMCWYRMSA-N 0.000 description 1
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- 238000006845 Michael addition reaction Methods 0.000 description 1
- AKUSQMQQAILABW-UHFFFAOYSA-N O=N.C1CN=CO1 Chemical compound O=N.C1CN=CO1 AKUSQMQQAILABW-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 208000032140 Sleepiness Diseases 0.000 description 1
- 206010041349 Somnolence Diseases 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 238000005882 aldol condensation reaction Methods 0.000 description 1
- 238000005575 aldol reaction Methods 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 229940025084 amphetamine Drugs 0.000 description 1
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 150000005829 chemical entities Chemical class 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- 229910000366 copper(II) sulfate Inorganic materials 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000036267 drug metabolism Effects 0.000 description 1
- 230000005518 electrochemistry Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-N formic acid Substances OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 1
- VANNPISTIUFMLH-UHFFFAOYSA-N glutaric anhydride Chemical compound O=C1CCCC(=O)O1 VANNPISTIUFMLH-UHFFFAOYSA-N 0.000 description 1
- MHAJPDPJQMAIIY-UHFFFAOYSA-N hydrogen peroxide Substances OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- 238000006198 methoxylation reaction Methods 0.000 description 1
- AORIUCNKPVHMTN-UHFFFAOYSA-N methyl 2,2-diphenylacetate Chemical class C=1C=CC=CC=1C(C(=O)OC)C1=CC=CC=C1 AORIUCNKPVHMTN-UHFFFAOYSA-N 0.000 description 1
- BNQRSYFOIRGRKV-UHFFFAOYSA-N methyl 2-(2-methoxyphenyl)acetate Chemical class COC(=O)CC1=CC=CC=C1OC BNQRSYFOIRGRKV-UHFFFAOYSA-N 0.000 description 1
- ZQYLDVNTWDEAJI-UHFFFAOYSA-N methyl 2-(4-methoxyphenyl)acetate Chemical class COC(=O)CC1=CC=C(OC)C=C1 ZQYLDVNTWDEAJI-UHFFFAOYSA-N 0.000 description 1
- SRIBJRZQDFBVQC-UHFFFAOYSA-N methyl 2-(4-phenylphenyl)acetate Chemical class C1=CC(CC(=O)OC)=CC=C1C1=CC=CC=C1 SRIBJRZQDFBVQC-UHFFFAOYSA-N 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000036651 mood Effects 0.000 description 1
- RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 1
- ODUCDPQEXGNKDN-UHFFFAOYSA-N nitroxyl Chemical compound O=N ODUCDPQEXGNKDN-UHFFFAOYSA-N 0.000 description 1
- 238000006772 olefination reaction Methods 0.000 description 1
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 229940093916 potassium phosphate Drugs 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 230000037321 sleepiness Effects 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- GIZSHQYTTBQKOQ-UHFFFAOYSA-N threo-Syringoylglycerol Chemical compound COC1=CC(C(O)C(O)CO)=CC(OC)=C1O GIZSHQYTTBQKOQ-UHFFFAOYSA-N 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
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CN104418797B (zh) * | 2013-08-26 | 2019-04-19 | 上海医药集团股份有限公司 | 哌甲酯、右哌甲酯的制备方法、其中间体及制备方法 |
WO2015069507A1 (en) * | 2013-11-08 | 2015-05-14 | Noramco, Inc. | Process for the preparation of methylphenidate and pharmaceutical salts thereof |
CN106432059A (zh) * | 2015-08-04 | 2017-02-22 | 上海朴颐化学科技有限公司 | 一种3-羟基哌啶和其衍生物的制备方法及其中间体 |
CN110105267A (zh) * | 2019-06-05 | 2019-08-09 | 南京焕然生物科技有限公司 | 一种右旋盐酸哌醋甲酯的制备方法 |
Citations (3)
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CN1709864A (zh) * | 2005-07-08 | 2005-12-21 | 成都科杰高新技术发展有限公司 | 一种紫杉醇及其类似物侧链的合成方法 |
CN1927830A (zh) * | 2006-10-24 | 2007-03-14 | 中国科学院成都生物研究所 | 光学纯亚磺酰胺化合物及其应用 |
CN101123965A (zh) * | 2005-01-20 | 2008-02-13 | 分子药物研究所公司 | 哌甲酯衍生物及其应用 |
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Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101123965A (zh) * | 2005-01-20 | 2008-02-13 | 分子药物研究所公司 | 哌甲酯衍生物及其应用 |
CN1709864A (zh) * | 2005-07-08 | 2005-12-21 | 成都科杰高新技术发展有限公司 | 一种紫杉醇及其类似物侧链的合成方法 |
CN1927830A (zh) * | 2006-10-24 | 2007-03-14 | 中国科学院成都生物研究所 | 光学纯亚磺酰胺化合物及其应用 |
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