CN106748695A - The preparation method of m-trifluoromethyl cinnamic acid - Google Patents
The preparation method of m-trifluoromethyl cinnamic acid Download PDFInfo
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- CN106748695A CN106748695A CN201611065709.5A CN201611065709A CN106748695A CN 106748695 A CN106748695 A CN 106748695A CN 201611065709 A CN201611065709 A CN 201611065709A CN 106748695 A CN106748695 A CN 106748695A
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- cinnamic acid
- trifluoromethylbenzaldehyde
- trifluoromethyl cinnamic
- acetaldehyde
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- KSBWHDDGWSYETA-SNAWJCMRSA-N (E)-3-(trifluoromethyl)cinnamic acid Chemical compound OC(=O)\C=C\C1=CC=CC(C(F)(F)F)=C1 KSBWHDDGWSYETA-SNAWJCMRSA-N 0.000 title claims abstract description 18
- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims abstract description 26
- NMTUHPSKJJYGML-UHFFFAOYSA-N 3-(trifluoromethyl)benzaldehyde Chemical compound FC(F)(F)C1=CC=CC(C=O)=C1 NMTUHPSKJJYGML-UHFFFAOYSA-N 0.000 claims abstract description 17
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims abstract description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims abstract description 14
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims abstract description 10
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000003054 catalyst Substances 0.000 claims abstract description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims abstract description 9
- 238000005575 aldol reaction Methods 0.000 claims abstract description 3
- 239000003960 organic solvent Substances 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- 150000001336 alkenes Chemical class 0.000 claims 2
- 238000009833 condensation Methods 0.000 claims 1
- 230000005494 condensation Effects 0.000 claims 1
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical group C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 abstract description 10
- 238000000034 method Methods 0.000 abstract description 7
- 238000006482 condensation reaction Methods 0.000 abstract description 5
- 238000006243 chemical reaction Methods 0.000 abstract description 3
- 238000009776 industrial production Methods 0.000 abstract description 2
- 230000000052 comparative effect Effects 0.000 description 11
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 8
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 4
- 229910052782 aluminium Inorganic materials 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 230000000977 initiatory effect Effects 0.000 description 4
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- 235000011121 sodium hydroxide Nutrition 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 238000005882 aldol condensation reaction Methods 0.000 description 2
- 239000004411 aluminium Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N formaldehyde Natural products O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 241000522254 Cassia Species 0.000 description 1
- OOCCDEMITAIZTP-QPJJXVBHSA-N Cinnamyl alcohol Natural products OC\C=C\C1=CC=CC=C1 OOCCDEMITAIZTP-QPJJXVBHSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- OOCCDEMITAIZTP-UHFFFAOYSA-N allylic benzylic alcohol Natural products OCC=CC1=CC=CC=C1 OOCCDEMITAIZTP-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- VDHAWDNDOKGFTD-MRXNPFEDSA-N cinacalcet Chemical compound N([C@H](C)C=1C2=CC=CC=C2C=CC=1)CCCC1=CC=CC(C(F)(F)F)=C1 VDHAWDNDOKGFTD-MRXNPFEDSA-N 0.000 description 1
- 229960003315 cinacalcet Drugs 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 239000012973 diazabicyclooctane Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 238000006197 hydroboration reaction Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- RDRCCJPEJDWSRJ-UHFFFAOYSA-N pyridine;1h-pyrrole Chemical compound C=1C=CNC=1.C1=CC=NC=C1 RDRCCJPEJDWSRJ-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000036632 reaction speed Effects 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000002910 solid waste Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
- C07C45/72—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups
- C07C45/74—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups combined with dehydration
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a kind of preparation method of m-trifluoromethyl cinnamic acid, it is obtained through a step aldol reaction in the presence of base catalyst with acetaldehyde by m-Trifluoromethylbenzaldehyde；Wherein, base catalyst is DBU, triethylamine or diisopropyl ethyl amine, and DBU is 1: 10~3: 5 with the mol ratio of m-Trifluoromethylbenzaldehyde；Acetaldehyde is 1: 1~5: 1 with the mol ratio of the m-Trifluoromethylbenzaldehyde；Condensation reaction is carried out in the presence of methyl alcohol, methyl tertiary butyl ether(MTBE) or tetrahydrofuran.Method of the present invention synthetic route is short, and reaction condition is gentle, simple to operate, especially by suitable base catalyst is selected, can obtain product of the purity more than 98% with preferable yield, so that it is adapted to large-scale industrial production, with larger application value.
Description
Technical field
The invention belongs to technology of fine chemicals, and in particular to a kind of preparation method of m-trifluoromethyl cinnamic acid.
Background technology
M-trifluoromethyl cinnamic acid is the important intermediate of synthetic hydrochloric acid cinacalcet.
The preparation method of m-trifluoromethyl cinnamic acid mainly has following several disclosed in prior art：
（One）With m-Trifluoromethylbenzaldehyde as initiation material, first m-TrifluoromethylcinnaAcid Acid is condensed to yield with acetic anhydride, then with
Piperidines is condensed to yield amide intermediate, is most obtained through red aluminium reducing afterwards.Its synthetic route is as follows：
。
（Two）With m-Trifluoromethylbenzaldehyde as initiation material, m-TrifluoromethylcinnaAcid Acid first is condensed to yield with malonic acid,
Activated ester intermediate is condensed to yield with carbonyl dimidazoles again, is most obtained through red aluminium reducing afterwards.Its synthetic route is as follows：
。
The deficiency of above two method is：（1）Synthetic route is more long, and total recovery is relatively low.（2）Reduction reaction is needed to use
Expensive red aluminum, does not only result in that production cost is higher, and the accessory substance post processing of red aluminum is more difficult.
（Three）With m-TrifluoromethylcinnaAcid Acid as initiation material, mixed anhydride first is condensed into ethyl chloroformate, then use hydroboration
Sodium reduction obtains m-trifluoromethyl cinnamyl alcohol, is finally aoxidized with manganese dioxide or TEMPO and obtained.Its synthetic route is as follows：
。
The deficiency of the method is：（1）Synthetic route is more long, and total recovery is relatively low, and production cost is higher.（2）Using boron hydrogen
Change sodium reduction to be difficult to control to.（3）More harmful solid waste can be produced using manganese dioxide.
（Four）With m-Trifluoromethylbenzaldehyde as initiation material, with acetaldehyde in the mixed solvent that aqueous slkali and ethanol are formed
Condensation reaction is carried out to obtain【Referring to Chinese patent literature CN104592037A】.Wherein, aqueous slkali be sodium hydrate aqueous solution or
Person's potassium hydroxide aqueous solution, its mass fraction is 1~3%；Aqueous slkali is 5~10: 1 with the volume ratio of ethanol；M-trifluoromethyl benzene
Formaldehyde is 1: 3.5~4.5 with the mol ratio of acetaldehyde；Setting-up point is 25~30 DEG C, and the reaction time is 5~10h.
The deficiency of the method is：Found using m-trifluoromethyl cinnamic acid obtained in the method through applicant's many experiments
Purity is relatively low, less than 90%.
The content of the invention
It is an object of the invention to solve the above problems, there is provided a kind of purity and yield m-trifluoromethyl Chinese cassia tree higher
The preparation method of aldehyde.
Realizing the technical scheme of above-mentioned purpose of the present invention is：A kind of preparation method of m-trifluoromethyl cinnamic acid, it be by
M-Trifluoromethylbenzaldehyde is obtained in the presence of base catalyst with acetaldehyde through a step aldol reaction.
Applicant is had found by numerous studies：The inorganic weak bases that the condensation reaction is commonly used using aldol condensation, such as sodium carbonate,
Potassium carbonate etc., reactionless phenomenon occurs；And the inorganic strong alkali commonly used using aldol condensation, such as NaOH, potassium hydroxide, hydrogen-oxygen
Change barium etc., the product of generation is more miscellaneous and is difficult to separate, and causes purity very low, less than 90%；And use conventional organic base, such as pyrrole
Pyridine, DMAP（DMAP）, 1,4- diazabicylos [2.2.2] octane（DABCO）Occur Deng same reactionless phenomenon.
Therefore, applicant finally found that by numerous studies：The condensation reaction is in the carbon -7- alkene of 1,8- diazabicylos 11
（DBU）, triethylamine or diisopropyl ethyl amine these three organic bases can obtain product of the purity more than 98%.
However, slower using triethylamine and diisopropyl ethyl amine reaction speed, the time is more long, and yield is relatively
It is low, therefore, base catalyst is preferably DBU.
Above-mentioned DBU is 1: 10~3: 5, preferably 1: 5 with the mol ratio of m-Trifluoromethylbenzaldehyde.
Above-mentioned acetaldehyde is 1: 1~5: 1, preferably 2.5: 1 with the mol ratio of m-Trifluoromethylbenzaldehyde.
Above-mentioned condensation reaction is carried out in presence of organic solvent；The organic solvent is methyl alcohol, methyl tertbutyl
Ether or tetrahydrofuran.
However, it is equally relatively low using methyl alcohol and methyl tertiary butyl ether(MTBE) yield, therefore, organic solvent is preferably tetrahydrochysene furan
Mutter.
The good effect that the present invention has：Method of the present invention synthetic route is short, and reaction condition is gentle, simple to operate, especially
It is, by selecting suitable base catalyst, can to obtain product of the purity more than 98% with preferable yield, so as to be adapted to
Large-scale industrial production, with larger application value.
Specific embodiment
（Embodiment 1）
The preparation method of the m-trifluoromethyl cinnamic acid of the present embodiment is as follows：
The m-Trifluoromethylbenzaldehyde of 17.41g is added in four-hole boiling flask（0.1mol）, 68.0mL tetrahydrofuran and
The DBU of 3.04g（0.02mol）, the 11.01g acetaldehyde of the lower fresh distillation of addition of stirring（0.25mol）, at room temperature（20~25 DEG C）
Stirring 48h, sampling is controlled in HPLC, is disappeared to raw material, terminates reaction.
Temperature of charge vacuum distillation less than 30 DEG C is kept, excessive acetaldehyde and solvent is removed, then adds that 1mol/L's is dilute
It is 3~5 that hydrochloric acid is neutralized to pH, is extracted with dichloromethane, and organic phase is concentrated under reduced pressure to remove solvent, and rectification under vacuum obtains colorless oil
Thing 15.0g, yield is 75.0%, and purity is 98.5%（HPLC）.
（2~embodiment of embodiment 7）
The preparation method of each embodiment is substantially the same manner as Example 1, and difference is shown in Table 1.
Table 1
| Embodiment 1 | Embodiment 2 | Embodiment 3 | Embodiment 4 | Embodiment 5 | Embodiment 6 | Embodiment 7 | |
| M-Trifluoromethylbenzaldehyde | 17.41g | 17.41g | 17.41g | 17.41g | 17.41g | 17.41g | 17.41g |
| Acetaldehyde | 11.01g | 11.01g | 11.01g | 11.01g | 11.01g | 11.01g | 11.01g |
| DBU | 3.04g | / | / | 3.04g | 3.04g | 1.52g | 9.12g |
| Triethylamine | / | 2.02g | / | / | / | / | / |
| Diisopropyl ethyl amine | / | / | 2.58g | / | / | / | / |
| Tetrahydrofuran | 68.0mL | 68.0mL | 68.0mL | / | / | 68.0mL | 68.0mL |
| Methyl alcohol | / | / | / | 68.0mL | / | / | / |
| Methyl tertiary butyl ether(MTBE) | / | / | / | / | 68.0mL | / | / |
| Weight | 15.0g | 11.4g | 12.4g | 10.8g | 13.6g | 14.0g | 14.8g |
| Purity | 98.5% | 98.1% | 98.2% | 98.0% | 98.3% | 98.4% | 98.6% |
| Yield | 75.0% | 57.0% | 62.0% | 54.0% | 68.0% | 70.0% | 74.0% |
（Comparative example 1 and comparative example 2）
Method according to Chinese patent literature CN104592037A embodiments 1 and embodiment 2 prepares m-trifluoromethyl cinnamic acid, knot
Fruit yield is respectively 70.3% and 69.7%, purity（HPLC）Respectively 87.2% and 85.9%.
（3~comparative example of comparative example 8）
The preparation method of each comparative example is substantially the same manner as Example 1, and difference is shown in Table 2.
Table 2
| Embodiment 1 | Comparative example 3 | Comparative example 4 | Comparative example 5 | Comparative example 6 | Comparative example 7 | Comparative example 8 | |
| M-Trifluoromethylbenzaldehyde | 17.41g | 17.41g | 17.41g | 17.41g | 17.41g | 17.41g | 17.41g |
| Acetaldehyde | 11.01g | 11.01g | 11.01g | 11.01g | 11.01g | 11.01g | 11.01g |
| DBU | 3.04g | 3.04g | / | / | / | / | / |
| NaOH | / | / | 0.8g | 0.8g | / | / | / |
| Potassium hydroxide | / | / | / | / | 1.12g | / | / |
| Potassium carbonate | / | / | / | / | / | 2.76g | / |
| DMAP | / | / | / | / | / | / | 2.44g |
| Tetrahydrofuran | 68.0mL | / | / | 68.0mL | 68.0mL | 68.0mL | 68.0mL |
| Ethanol | / | 68.0mL | 68.0mL | / | / | / | / |
| Products weight | 15.0g | 14.1g | 14.4g | 11.7g | 12.0g | Nothing | Nothing |
| Purity | 98.5% | 94.4% | 88.2% | 87.0% | 84.3% | / | / |
| Yield | 75.0% | 70.5% | 72.0% | 58.5% | 60.0% | / | / |
Claims (8)
1. a kind of preparation method of m-trifluoromethyl cinnamic acid, it is in base catalyst by m-Trifluoromethylbenzaldehyde and acetaldehyde
In the presence of through a step aldol reaction be obtained；It is characterized in that：The base catalyst is 1,8- diazabicylos 11
Carbon -7- alkene, triethylamine or diisopropyl ethyl amine.
2. the preparation method of m-trifluoromethyl cinnamic acid according to claim 1, it is characterised in that：The base catalyst
It is the carbon -7- alkene of 1,8- diazabicylos 11.
3. the preparation method of m-trifluoromethyl cinnamic acid according to claim 1 and 2, it is characterised in that：The 1,8- bis-
Carbon -7- the alkene of azabicyclic 11 is 1: 10~3: 5 with the mol ratio of the m-Trifluoromethylbenzaldehyde.
4. the preparation method of m-trifluoromethyl cinnamic acid according to claim 3, it is characterised in that：The 1,8- diazas
Carbon -7- the alkene of two ring 11 is 1: 5 with the mol ratio of the m-Trifluoromethylbenzaldehyde.
5. the preparation method of m-trifluoromethyl cinnamic acid according to claim 1 and 2, it is characterised in that：The acetaldehyde with
The mol ratio of the m-Trifluoromethylbenzaldehyde is 1: 1~5: 1.
6. the preparation method of m-trifluoromethyl cinnamic acid according to claim 5, it is characterised in that：The acetaldehyde with it is described
The mol ratio of m-Trifluoromethylbenzaldehyde is 2.5: 1.
7. the preparation method of m-trifluoromethyl cinnamic acid according to claim 1 and 2, it is characterised in that：The condensation is
Carry out in presence of organic solvent；The organic solvent is methyl alcohol, methyl tertiary butyl ether(MTBE) or tetrahydrofuran.
8. the preparation method of m-trifluoromethyl cinnamic acid according to claim 7, it is characterised in that：The organic solvent is
Tetrahydrofuran.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN112830879A (en) * | 2019-11-22 | 2021-05-25 | 北京泰德制药股份有限公司 | Preparation method of cinacalcet hydrochloride |
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| CN104592037A (en) * | 2015-01-08 | 2015-05-06 | 浙江大学 | Synthesis method of cinacalcet |
| CN105646215A (en) * | 2008-04-09 | 2016-06-08 | 杜邦公司 | Method for preparing 3-trifluoromethyl chalcones |
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2016
- 2016-11-28 CN CN201611065709.5A patent/CN106748695B/en active Active
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| Publication number | Priority date | Publication date | Assignee | Title |
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