CN104649934A - 一种医药中间体三氟甲基取代芳烃类化合物的合成方法 - Google Patents
一种医药中间体三氟甲基取代芳烃类化合物的合成方法 Download PDFInfo
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- CN104649934A CN104649934A CN201510072763.1A CN201510072763A CN104649934A CN 104649934 A CN104649934 A CN 104649934A CN 201510072763 A CN201510072763 A CN 201510072763A CN 104649934 A CN104649934 A CN 104649934A
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 title claims abstract description 31
- 238000000034 method Methods 0.000 title claims abstract description 14
- 150000001491 aromatic compounds Chemical class 0.000 title abstract 4
- 230000002194 synthesizing effect Effects 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 33
- 238000006243 chemical reaction Methods 0.000 claims abstract description 31
- 239000003513 alkali Substances 0.000 claims abstract description 15
- 238000003756 stirring Methods 0.000 claims abstract description 12
- 239000003960 organic solvent Substances 0.000 claims abstract description 11
- 125000004185 ester group Chemical group 0.000 claims abstract description 4
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 4
- 150000002367 halogens Chemical class 0.000 claims abstract description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 30
- 238000010189 synthetic method Methods 0.000 claims description 30
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 27
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 26
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 claims description 22
- 239000004332 silver Substances 0.000 claims description 22
- 229910052709 silver Inorganic materials 0.000 claims description 22
- -1 arene compounds Chemical class 0.000 claims description 18
- CMGDVUCDZOBDNL-UHFFFAOYSA-N 4-methyl-2h-benzotriazole Chemical compound CC1=CC=CC2=NNN=C12 CMGDVUCDZOBDNL-UHFFFAOYSA-N 0.000 claims description 17
- YSSSPARMOAYJTE-UHFFFAOYSA-N dibenzo-18-crown-6 Chemical compound O1CCOCCOC2=CC=CC=C2OCCOCCOC2=CC=CC=C21 YSSSPARMOAYJTE-UHFFFAOYSA-N 0.000 claims description 14
- 239000012046 mixed solvent Substances 0.000 claims description 11
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 9
- IBWXIFXUDGADCV-UHFFFAOYSA-N 2h-benzotriazole;silver Chemical compound [Ag].C1=CC=C2NN=NC2=C1 IBWXIFXUDGADCV-UHFFFAOYSA-N 0.000 claims description 6
- 238000010898 silica gel chromatography Methods 0.000 claims description 6
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 5
- 238000004821 distillation Methods 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- 238000009413 insulation Methods 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 239000012074 organic phase Substances 0.000 claims description 5
- 239000000243 solution Substances 0.000 claims description 5
- 238000010792 warming Methods 0.000 claims description 5
- 238000005406 washing Methods 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 4
- SHLCGTACJPPATG-UHFFFAOYSA-N butanedioic acid;silver Chemical compound [Ag].OC(=O)CCC(O)=O SHLCGTACJPPATG-UHFFFAOYSA-N 0.000 claims description 3
- XIBQIEXKKBNYOT-UHFFFAOYSA-N phthalic acid;silver Chemical compound [Ag].OC(=O)C1=CC=CC=C1C(O)=O XIBQIEXKKBNYOT-UHFFFAOYSA-N 0.000 claims description 3
- NBYLLBXLDOPANK-UHFFFAOYSA-M silver 2-carboxyphenolate hydrate Chemical compound C1=CC=C(C(=C1)C(=O)O)[O-].O.[Ag+] NBYLLBXLDOPANK-UHFFFAOYSA-M 0.000 claims description 3
- WZHHYIOUKQNLQM-UHFFFAOYSA-N 3,4,5,6-tetrachlorophthalic acid Chemical compound OC(=O)C1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1C(O)=O WZHHYIOUKQNLQM-UHFFFAOYSA-N 0.000 claims description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 2
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 2
- 238000006692 trifluoromethylation reaction Methods 0.000 abstract description 10
- 239000000758 substrate Substances 0.000 abstract description 7
- 239000003054 catalyst Substances 0.000 abstract description 5
- 238000010438 heat treatment Methods 0.000 abstract 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 1
- 238000004321 preservation Methods 0.000 abstract 1
- 239000003153 chemical reaction reagent Substances 0.000 description 14
- 239000003814 drug Substances 0.000 description 10
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 9
- 239000000543 intermediate Substances 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 5
- 239000002904 solvent Substances 0.000 description 4
- 238000004293 19F NMR spectroscopy Methods 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- 241001120493 Arene Species 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 150000001448 anilines Chemical class 0.000 description 2
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N benzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000012450 pharmaceutical intermediate Substances 0.000 description 2
- XQQZRZQVBFHBHL-UHFFFAOYSA-N 12-crown-4 Chemical compound C1COCCOCCOCCO1 XQQZRZQVBFHBHL-UHFFFAOYSA-N 0.000 description 1
- SOZGHDCEWOLLHV-UHFFFAOYSA-N 2-(trifluoromethyl)benzonitrile Chemical compound FC(F)(F)C1=CC=CC=C1C#N SOZGHDCEWOLLHV-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- GYWJXHZSEFFBHZ-UHFFFAOYSA-N Nc(cccc1)c1[Zn] Chemical compound Nc(cccc1)c1[Zn] GYWJXHZSEFFBHZ-UHFFFAOYSA-N 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 150000003983 crown ethers Chemical class 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 150000002390 heteroarenes Chemical class 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- DYIZHKNUQPHNJY-UHFFFAOYSA-N oxorhenium Chemical compound [Re]=O DYIZHKNUQPHNJY-UHFFFAOYSA-N 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- QRUBYZBWAOOHSV-UHFFFAOYSA-M silver trifluoromethanesulfonate Chemical compound [Ag+].[O-]S(=O)(=O)C(F)(F)F QRUBYZBWAOOHSV-UHFFFAOYSA-M 0.000 description 1
- ZYXPMOIHQRKWGT-UHFFFAOYSA-N silver;2,2,2-trifluoroacetic acid Chemical compound [Ag].OC(=O)C(F)(F)F ZYXPMOIHQRKWGT-UHFFFAOYSA-N 0.000 description 1
- QUVCHIHRXFRSGU-UHFFFAOYSA-N silver;3,4,5,6-tetrachlorophthalic acid Chemical compound [Ag].OC(=O)C1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1C(O)=O QUVCHIHRXFRSGU-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
Description
Claims (10)
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CN201510072763.1A CN104649934B (zh) | 2015-02-12 | 2015-02-12 | 一种医药中间体三氟甲基取代芳烃类化合物的合成方法 |
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CN201510072763.1A CN104649934B (zh) | 2015-02-12 | 2015-02-12 | 一种医药中间体三氟甲基取代芳烃类化合物的合成方法 |
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CN104649934A true CN104649934A (zh) | 2015-05-27 |
CN104649934B CN104649934B (zh) | 2016-05-18 |
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105541685A (zh) * | 2016-02-22 | 2016-05-04 | 李青阁 | 一种三氟甲基取代亚砜化合物的合成方法 |
CN105669509A (zh) * | 2016-02-22 | 2016-06-15 | 李青阁 | 一种亚砜化合物的改进合成方法 |
-
2015
- 2015-02-12 CN CN201510072763.1A patent/CN104649934B/zh not_active Expired - Fee Related
Non-Patent Citations (4)
Title |
---|
RAFFAEL KOLLER, ET AL: "Zinc-Mediated Formation of Trifluoromethyl Ethers from Alcohols and Hypervalent Iodine Trifluoromethylation Reagents", 《ANGEW. CHEM. INT. ED.》, vol. 48, 11 May 2009 (2009-05-11), pages 4332 - 4336 * |
SANGWON SEO, ET AL.,: "Silver-catalysed trifluoromethylation of arenes at room temperature", 《CHEM. COMMUN.》, vol. 49, 17 May 2013 (2013-05-17), pages 6385 - 6387 * |
TERUO UMEMOTO, ET AL.: "Synthesis and Reactivity of N-Trifluoromethyl-N-nitrosotrifluoromethanesulfonamide as a New Type of Frifluoromethylation Agent", 《BULL. CHEM. SOC. JPN.》, vol. 59, 28 February 1986 (1986-02-28), pages 447 - 452 * |
YINGDAYE, ET AL.: "Silver-Mediated Trifluoromethylation of Arenes Using TMSCF", 《ORG. LETT.》, vol. 13, no. 20, 20 September 2011 (2011-09-20), pages 5464 - 5467 * |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105541685A (zh) * | 2016-02-22 | 2016-05-04 | 李青阁 | 一种三氟甲基取代亚砜化合物的合成方法 |
CN105669509A (zh) * | 2016-02-22 | 2016-06-15 | 李青阁 | 一种亚砜化合物的改进合成方法 |
CN105669509B (zh) * | 2016-02-22 | 2017-11-07 | 陈玉玲 | 一种亚砜化合物的改进合成方法 |
CN105541685B (zh) * | 2016-02-22 | 2017-11-14 | 陈玉玲 | 一种三氟甲基取代亚砜化合物的合成方法 |
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Inventor after: Li Yibiao Inventor after: Pan Meiling Inventor after: Pan Meixia Inventor before: Zhang Yan Inventor before: Yang Haixia |
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Effective date of registration: 20160420 Address after: Industrial Park, Gu Yong Zhen Ji Shan Fujian province 353300 Sanming City Jiangle County Applicant after: FUJIAN WANKE PHARMACEUTICAL CO., LTD. Address before: 201112 Minhang District Pu Pu Road, Lane 598, Lane 201, room 12, No. Applicant before: Yang Haixia |
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