CN113563242A - 一种3-(2,2,2-三氟乙基)-吡咯烷盐酸盐的制备方法 - Google Patents
一种3-(2,2,2-三氟乙基)-吡咯烷盐酸盐的制备方法 Download PDFInfo
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- CN113563242A CN113563242A CN202110813487.5A CN202110813487A CN113563242A CN 113563242 A CN113563242 A CN 113563242A CN 202110813487 A CN202110813487 A CN 202110813487A CN 113563242 A CN113563242 A CN 113563242A
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- Prior art keywords
- trifluoroethyl
- benzyl
- reaction
- methanol
- dissolving
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- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- HUYFAOPHHUVGEM-UHFFFAOYSA-N 3-(2,2,2-trifluoroethyl)pyrrolidine;hydrochloride Chemical compound Cl.FC(F)(F)CC1CCNC1 HUYFAOPHHUVGEM-UHFFFAOYSA-N 0.000 title claims abstract description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 111
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 claims abstract description 30
- 239000003054 catalyst Substances 0.000 claims abstract description 26
- UPJARUPXOIJDJY-UHFFFAOYSA-N 1-benzyl-3-(2,2,2-trifluoroethyl)pyrrolidine Chemical compound C1CN(CC1CC(F)(F)F)CC2=CC=CC=C2 UPJARUPXOIJDJY-UHFFFAOYSA-N 0.000 claims abstract description 19
- VZAUGXGQJXAJPY-UHFFFAOYSA-N 1-benzyl-3-(2,2,2-trifluoroethyl)pyrrolidin-2-one Chemical compound O=C1N(CC2=CC=CC=C2)CCC1CC(F)(F)F VZAUGXGQJXAJPY-UHFFFAOYSA-N 0.000 claims abstract description 17
- LVUQCTGSDJLWCE-UHFFFAOYSA-N 1-benzylpyrrolidin-2-one Chemical compound O=C1CCCN1CC1=CC=CC=C1 LVUQCTGSDJLWCE-UHFFFAOYSA-N 0.000 claims abstract description 17
- 238000000034 method Methods 0.000 claims abstract description 15
- 239000001257 hydrogen Substances 0.000 claims abstract description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 12
- 239000000376 reactant Substances 0.000 claims abstract description 12
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 claims abstract description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 7
- 238000006467 substitution reaction Methods 0.000 claims abstract description 6
- 229910000085 borane Inorganic materials 0.000 claims abstract description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 81
- 239000000243 solution Substances 0.000 claims description 46
- 238000006243 chemical reaction Methods 0.000 claims description 45
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 28
- 239000002904 solvent Substances 0.000 claims description 26
- 239000000706 filtrate Substances 0.000 claims description 24
- 238000001914 filtration Methods 0.000 claims description 23
- 239000012074 organic phase Substances 0.000 claims description 23
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 20
- 238000001816 cooling Methods 0.000 claims description 18
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 16
- 238000001035 drying Methods 0.000 claims description 16
- UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 claims description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 14
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 13
- 239000007864 aqueous solution Substances 0.000 claims description 11
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 10
- 230000035484 reaction time Effects 0.000 claims description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 10
- WORJRXHJTUTINR-UHFFFAOYSA-N 1,4-dioxane;hydron;chloride Chemical compound Cl.C1COCCO1 WORJRXHJTUTINR-UHFFFAOYSA-N 0.000 claims description 9
- 239000012043 crude product Substances 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 8
- 238000010791 quenching Methods 0.000 claims description 8
- 238000004440 column chromatography Methods 0.000 claims description 7
- 239000012071 phase Substances 0.000 claims description 7
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 5
- 238000004108 freeze drying Methods 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 5
- 230000000171 quenching effect Effects 0.000 claims description 5
- 238000005406 washing Methods 0.000 claims description 5
- 239000008346 aqueous phase Substances 0.000 claims description 3
- 238000000605 extraction Methods 0.000 claims description 2
- 230000007935 neutral effect Effects 0.000 claims description 2
- 239000011541 reaction mixture Substances 0.000 claims 1
- PTXOIRIEXVHPML-UHFFFAOYSA-N 3-(2,2,2-trifluoroethyl)pyrrolidine Chemical compound FC(F)(F)CC1CCNC1 PTXOIRIEXVHPML-UHFFFAOYSA-N 0.000 abstract description 5
- 239000000047 product Substances 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 239000011259 mixed solution Substances 0.000 description 6
- 239000002994 raw material Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000012295 chemical reaction liquid Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 2
- 239000012025 fluorinating agent Substances 0.000 description 2
- UTMIEQASUFFADK-UHFFFAOYSA-N 3,3,3-trifluoropropanal Chemical compound FC(F)(F)CC=O UTMIEQASUFFADK-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- JAEIBKXSIXOLOL-UHFFFAOYSA-N pyrrolidin-1-ium-3-carboxylate Chemical compound OC(=O)C1CCNC1 JAEIBKXSIXOLOL-UHFFFAOYSA-N 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- QHMQWEPBXSHHLH-UHFFFAOYSA-N sulfur tetrafluoride Chemical compound FS(F)(F)F QHMQWEPBXSHHLH-UHFFFAOYSA-N 0.000 description 1
- BFKJFAAPBSQJPD-UHFFFAOYSA-N tetrafluoroethene Chemical group FC(F)=C(F)F BFKJFAAPBSQJPD-UHFFFAOYSA-N 0.000 description 1
- 239000002341 toxic gas Substances 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyrrole Compounds (AREA)
Abstract
Description
Claims (10)
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110813487.5A CN113563242A (zh) | 2021-07-19 | 2021-07-19 | 一种3-(2,2,2-三氟乙基)-吡咯烷盐酸盐的制备方法 |
PCT/CN2022/106174 WO2023001088A1 (en) | 2021-07-19 | 2022-07-18 | Preparation method of 3- (2, 2, 2-trifluoroethyl) pyrrolidine hydrochloride |
CA3225631A CA3225631A1 (en) | 2021-07-19 | 2022-07-18 | Preparation method of 3- (2, 2, 2-trifluoroethyl) pyrrolidine hydrochloride |
EP22845253.8A EP4373806A1 (en) | 2021-07-19 | 2022-07-18 | Preparation method of 3- (2, 2, 2-trifluoroethyl) pyrrolidine hydrochloride |
AU2022314815A AU2022314815A1 (en) | 2021-07-19 | 2022-07-18 | Preparation method of 3- (2, 2, 2-trifluoroethyl) pyrrolidine hydrochloride |
Applications Claiming Priority (1)
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CN202110813487.5A CN113563242A (zh) | 2021-07-19 | 2021-07-19 | 一种3-(2,2,2-三氟乙基)-吡咯烷盐酸盐的制备方法 |
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2023001088A1 (en) * | 2021-07-19 | 2023-01-26 | Kinnate Biopharma Inc. | Preparation method of 3- (2, 2, 2-trifluoroethyl) pyrrolidine hydrochloride |
CN117142918A (zh) * | 2022-12-30 | 2023-12-01 | 北京师范大学 | 一种含手性三氟甲基氮杂环化合物的制备方法 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006128692A2 (en) * | 2005-06-01 | 2006-12-07 | Ucb Pharma, S.A. | 2-oxo-1-pyrrolidine derivatives and their therapeutic use on the central nervous system |
CN103857670A (zh) * | 2011-10-11 | 2014-06-11 | Ucb医药有限公司 | 2-氧代-哌啶基衍生物 |
-
2021
- 2021-07-19 CN CN202110813487.5A patent/CN113563242A/zh active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006128692A2 (en) * | 2005-06-01 | 2006-12-07 | Ucb Pharma, S.A. | 2-oxo-1-pyrrolidine derivatives and their therapeutic use on the central nervous system |
CN103857670A (zh) * | 2011-10-11 | 2014-06-11 | Ucb医药有限公司 | 2-氧代-哌啶基衍生物 |
Non-Patent Citations (2)
Title |
---|
BUGERA,MAKSYM等: "Deoxofluorination of Aliphatic Carboxylic Acids: A Route to Trifluoromethyl-Substituted Derivatives.", 《J. ORG. CHEM.》 * |
WANG,ZENG等: "Aluminium Chloride-Mediated Synthesis of 1-Chloro-2,2,2-Trifluoroethylidene-Substituted Pyrrolidones.", 《ADV. SYNTH. CATAL.》 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2023001088A1 (en) * | 2021-07-19 | 2023-01-26 | Kinnate Biopharma Inc. | Preparation method of 3- (2, 2, 2-trifluoroethyl) pyrrolidine hydrochloride |
CN117142918A (zh) * | 2022-12-30 | 2023-12-01 | 北京师范大学 | 一种含手性三氟甲基氮杂环化合物的制备方法 |
CN117142918B (zh) * | 2022-12-30 | 2024-02-02 | 北京师范大学 | 一种含手性三氟甲基氮杂环化合物的制备方法 |
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Effective date of registration: 20220421 Address after: 201322 room 402-a, building 1, No. 1199, indigo Road, Pudong New Area, Shanghai Applicant after: Du Chuang (Shanghai) Medical Technology Co.,Ltd. Address before: 710000 south side of floor 7, block C, No. 999, caotan 10th Road, caotan Ecological Industrial Park, economic and Technological Development Zone, Xi'an, Shaanxi Province Applicant before: Xi'an Duchuang Pharmaceutical Technology Co.,Ltd. |
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Effective date of registration: 20220809 Address after: California, USA Applicant after: Jinnaite biopharmaceutical Co. Address before: 201322 room 402-a, building 1, No. 1199, indigo Road, Pudong New Area, Shanghai Applicant before: Du Chuang (Shanghai) Medical Technology Co.,Ltd. |
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