CN102701949A - Method for preparing 2-[4-(2-methyl-1-propenyl)phenyl]propionic acid - Google Patents
Method for preparing 2-[4-(2-methyl-1-propenyl)phenyl]propionic acid Download PDFInfo
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- methyl isophthalic
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- 238000000034 method Methods 0.000 title abstract description 16
- WYUJTWQSJJRVIG-UHFFFAOYSA-N 2-[4-(2-methylprop-1-enyl)phenyl]propanoic acid Chemical compound OC(=O)C(C)C1=CC=C(C=C(C)C)C=C1 WYUJTWQSJJRVIG-UHFFFAOYSA-N 0.000 title abstract 3
- 238000006243 chemical reaction Methods 0.000 claims abstract description 40
- 238000006482 condensation reaction Methods 0.000 claims abstract description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 73
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 38
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 33
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 24
- 235000019260 propionic acid Nutrition 0.000 claims description 16
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 16
- 239000000243 solution Substances 0.000 claims description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 15
- URQKFBFYKBBRRH-UHFFFAOYSA-N C1(=CC=CC=C1)C=CC.CC1=C(C(=O)O)C=CC=C1C(=O)O Chemical group C1(=CC=CC=C1)C=CC.CC1=C(C(=O)O)C=CC=C1C(=O)O URQKFBFYKBBRRH-UHFFFAOYSA-N 0.000 claims description 11
- 238000006460 hydrolysis reaction Methods 0.000 claims description 11
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 claims description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Substances CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 10
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 10
- 238000000605 extraction Methods 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 10
- 230000007062 hydrolysis Effects 0.000 claims description 9
- JEQDSBVHLKBEIZ-UHFFFAOYSA-N 2-chloropropanoyl chloride Chemical compound CC(Cl)C(Cl)=O JEQDSBVHLKBEIZ-UHFFFAOYSA-N 0.000 claims description 8
- 238000010792 warming Methods 0.000 claims description 8
- 238000005727 Friedel-Crafts reaction Methods 0.000 claims description 5
- 238000010992 reflux Methods 0.000 claims description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 5
- 238000005406 washing Methods 0.000 claims description 5
- 239000011787 zinc oxide Substances 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 claims description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 238000006462 rearrangement reaction Methods 0.000 claims description 4
- JXKPEJDQGNYQSM-UHFFFAOYSA-M sodium propionate Chemical compound [Na+].CCC([O-])=O JXKPEJDQGNYQSM-UHFFFAOYSA-M 0.000 claims description 4
- 235000010334 sodium propionate Nutrition 0.000 claims description 4
- 239000004324 sodium propionate Substances 0.000 claims description 4
- 229960003212 sodium propionate Drugs 0.000 claims description 4
- 230000008707 rearrangement Effects 0.000 claims description 3
- 230000020477 pH reduction Effects 0.000 claims description 2
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 abstract description 10
- 229960001680 ibuprofen Drugs 0.000 abstract description 10
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 2
- 239000007795 chemical reaction product Substances 0.000 abstract 2
- 238000001514 detection method Methods 0.000 abstract 2
- BTOVVHWKPVSLBI-UHFFFAOYSA-N 2-methylprop-1-enylbenzene Chemical compound CC(C)=CC1=CC=CC=C1 BTOVVHWKPVSLBI-UHFFFAOYSA-N 0.000 abstract 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 abstract 1
- 230000003301 hydrolyzing effect Effects 0.000 abstract 1
- SLCVBVWXLSEKPL-UHFFFAOYSA-N neopentyl glycol Chemical compound OCC(C)(C)CO SLCVBVWXLSEKPL-UHFFFAOYSA-N 0.000 abstract 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
- 239000000463 material Substances 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 238000005352 clarification Methods 0.000 description 3
- 239000002027 dichloromethane extract Substances 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000012452 mother liquor Substances 0.000 description 3
- KXXXUIKPSVVSAW-UHFFFAOYSA-K pyranine Chemical compound [Na+].[Na+].[Na+].C1=C2C(O)=CC(S([O-])(=O)=O)=C(C=C3)C2=C2C3=C(S([O-])(=O)=O)C=C(S([O-])(=O)=O)C2=C1 KXXXUIKPSVVSAW-UHFFFAOYSA-K 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- XQXPVVBIMDBYFF-UHFFFAOYSA-N 4-hydroxyphenylacetic acid Chemical compound OC(=O)CC1=CC=C(O)C=C1 XQXPVVBIMDBYFF-UHFFFAOYSA-N 0.000 description 2
- 238000003747 Grignard reaction Methods 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000007670 refining Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- ZHMMPVANGNPCBW-UHFFFAOYSA-N 4-Hydroxyhydratropate Chemical compound OC(=O)C(C)C1=CC=C(O)C=C1 ZHMMPVANGNPCBW-UHFFFAOYSA-N 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- JXLHNMVSKXFWAO-UHFFFAOYSA-N azane;7-fluoro-2,1,3-benzoxadiazole-4-sulfonic acid Chemical compound N.OS(=O)(=O)C1=CC=C(F)C2=NON=C12 JXLHNMVSKXFWAO-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to the field of organic synthesis, in particular to a novel method for preparing 2-[4-(2-methyl-1-propenyl)phenyl]propionic acid, which comprises the following steps: performing Frieldel-Crafts reaction between 2-methyl-1-phenyl propene with alpha-chloropropinoyl chloride, secondly, performing condensation reaction between the reaction product and neopentyl glycol, and finally, rearranging, hydrolyzing and acidizing the finally obtained reaction product to obtain the 2-[4-(2-methyl-1-propenyl)phenyl]propionic acid. The method has a simple process and is convenient to operate; compared with the prior art, the method has a higher yield and a relatively low cost, requires no extreme reaction condition and valuable reagent and is mild and controllable; and furthermore, because the method is similar to the synthesis process of ibuprofen, the detection of each intermediate can refer to the detection process of ibuprofen; and therefore, the method is easy to implement.
Description
Technical field
The present invention relates to the organic synthesis field, be specifically related to a kind of 2-[4-(2-methyl isophthalic acid-propenyl) phenyl] preparation method that propionic acid is new.
Background technology
2-[4-(2-methyl isophthalic acid-propenyl) phenyl] propionic acid is the micro-related substance that exists in the non-steroidal anti-inflammation and analgesic drugs Ibuprofen BP/EP, the similar of it and Ibuprofen BP/EP, and difference is many two keys, the two structure is following:
2-[4-(2-methyl isophthalic acid-propenyl) phenyl] propionic acid Ibuprofen BP/EP
As the related substance in the Ibuprofen BP/EP, need highly purified 2-[4-(2-methyl isophthalic acid-propenyl) phenyl] propionic acid in daily production and the scientific research.This material does not have commodity selling at present, for this reason with reference to the Ibuprofen BP/EP production technique, designs a new 2-[4-(2-methyl isophthalic acid-propenyl) phenyl] propionic acid synthesis technique and achieves success, and Ibuprofen BP/EP production and scientific research are had great significance.
The method for preparing 2-[4-(2-methyl isophthalic acid-propenyl) phenyl] propionic acid of bibliographical information mainly contains: WO2011051375; EP2316820; J.Med.C, 50 (17), documents such as 3984-4002 are that starting raw material prepares title product with the p-hydroxyphenylaceticacid, but used methyl iodide in the reaction process, valuable raw material such as trifluoro sulphonate, temperature of reaction is-78 ℃, condition is harsh.
J.Med.C, 48 (13), 4312-4331; J.Med.C, 50 (17), documents such as 3984-4002 are that starting raw material prepares title product with the Alpha-Methyl p-hydroxyphenylaceticacid, and are similar with article one route method, condition is gentle a little, but cost is high equally.
Chem.Pharm.Bull.34 (11), 4653-4662; To be starting raw material to chlorobenzene, make grignard reagent, make 1-butylene base-4-chlorobenzene through grignard reaction, with the ethyl bromide reaction, hydrolysis gets title product, has used reactions step more rambunctious such as grignard reaction in the whole process again, and yield is low, and cost is high.
Summary of the invention
Problem to be solved by this invention has provided the preparation method of a kind of 2-[4-(2-methyl isophthalic acid-propenyl) phenyl] propionic acid; Adopt 2-methyl isophthalic acid-phenyl propylene and alpha-chloro propionyl chloride through friedel-crafts reaction; Again with the NSC 6366 condensation reaction; Make through rearrangement, hydrolysis, acidifying, its reaction temperature is low with, yield height and cost.
The preparation method of 2-of the present invention [4-(2-methyl isophthalic acid-propenyl) phenyl] propionic acid, be with 2-methyl isophthalic acid-phenyl propylene and alpha-chloro propionyl chloride through friedel-crafts reaction, with the NSC 6366 condensation reaction, make again through rearrangement, hydrolysis, acidifying.
The present invention specifically may further comprise the steps:
(1) friedel-crafts reaction: aluminum chloride is dissolved in the methylene dichloride, and-5～0 ℃ drips the alpha-chloro propionyl chloride, reaction.Reaction finishes, and-5～0 ℃ drips 2-methyl isophthalic acid-phenyl propylene, reaction.Reaction finishes, hydrolysis, and dichloromethane extraction, methylene dichloride is reclaimed in washing, gets 1-[4-(2-methyl isophthalic acid-propenyl) phenyl]-2-chloro-1-acetone (A).
(2) condensation reaction: in the NSC 6366 toluene solution; Add tosic acid, 1-[4-(2-methyl isophthalic acid-propenyl) phenyl]-2-chloro-1-acetone; 100～115 ℃ of band water reactions that reflux; Get 2-(2-chloropropyl)-2-[4-(2-methyl isophthalic acid-propenyl) phenyl]-5,5-dimethyl--1, the toluene solution of 3-dioxane (B).
(3) rearrangement reaction: 2-(2-chloropropyl)-2-[4-(2-methyl isophthalic acid-propenyl) phenyl]-5; 5-dimethyl--1; The toluene solution of 3-dioxane (B) steams toluene to 115～120 ℃, adds zinc oxide, is warming up to 140～160 ℃ and carries out rearrangement reaction; Get the toluene solution of (2,2-dimethyl--3-chlorine) propyl group-2-[4-(2-methyl isophthalic acid-propenyl) phenyl] propionic ester (C).
(4) hydrolysis reaction: (2; 2-dimethyl--3-chlorine) toluene solution of propyl group-2-[4-(2-methyl isophthalic acid-propenyl) phenyl] propionic ester (C) is cooled to 65 ~ 75 ℃, adds NaOH, and 70～85 ℃ are hydrolyzed; Finish; Add water, add methylbenzene extraction again, get 2-[4-(2-methyl isophthalic acid-propenyl) phenyl] Sodium Propionate (D) aqueous solution.
(5) acidification reaction: 2-[4-(2-methyl isophthalic acid-propenyl) phenyl] Sodium Propionate (D) aqueous solution gets 2-[4-(2-methyl isophthalic acid-propenyl) phenyl] propionic acid (E) with hcl acidifying.
(6) refining: 2-[4-(2-methyl isophthalic acid-propenyl) phenyl] propionic acid (E) bullion is refining with normal hexane, gets the product of purity more than 99%.
Reaction equation is following:
Step of the present invention (5) can obtain the title product of purity more than 95% when finishing, and selects normal hexane for use, can obtain purity 99% above title product through a recrystallization.
Beneficial effect of the present invention is following:
Technology of the present invention is simple, processing ease, and compared with prior art, yield is higher, cost is relatively low; There is not harsh reaction conditions, gentle controlled; There is not valuable reagent; Because similar with the Ibuprofen BP/EP synthesis technique, each midbody detects all can be with reference to the Ibuprofen BP/EP characterization processes, easy to implement.
Embodiment
Below in conjunction with embodiment the present invention is done and to further describe.
Embodiment 1
In the reaction flask of clean dried, drop into 6.8ml methylene dichloride, 7g aluminum chloride, stir and cool to-5 ℃, drip 6 gram alpha-chloro propionyl chlorides, drip off, kept this thermotonus 20 minutes;-3 ℃, nitrogen protection, Dropwise 5 gram 2-methyl isophthalic acid-phenyl propylene drips off, and keeps this thermotonus 1 hour.Reaction solution is added the reaction that is hydrolyzed in the frozen water, and hydrolysis temperature is controlled at 10 ℃.Hydrolyzed solution leaves standstill, separatory.Water layer is with 10ml dichloromethane extraction one time.The dichloromethane extract and the bed of material merge, with water washing 3 times, and each water 16ml.Reclaim methylene dichloride, get blackish green 8 gram 1-[4-(2-methyl isophthalic acid-propenyl) phenyl]-2-chloro-1-acetone, yield 97%, gc is surveyed content greater than 95%.
In reaction flask, add 6 gram NSC 6366s, 20ml toluene, nitrogen replacement is warming up to 50 ℃ and adds 1 gram tosic acid, 8 gram 1-[4-(2-methyl isophthalic acid-propenyl) phenyl]-2-chloro-1-acetone, and 115 ℃ of band water reactions that reflux are to clarification.
Steam toluene to 120 ℃, add 0.2 gram zinc oxide, continue to be warming up to 150 ℃ of reactions 1 hour.
Cool to 70 ℃, add 4ml 30%NaOH, keep 70 ℃ of reactions 2 hours, reduce to room temperature, left standstill 1 hour, inhale and remove the upper strata mother liquor; Add 20ml water dissolution solid, add the 10ml*3 methylbenzene extraction, divide and remove toluene layer.
Water layer, filters to PH5～6 with 30% hcl acidifying, obtains 6 gram 2-[4-(2-methyl isophthalic acid-propenyl) phenyl] propionic acid, collects rate 77% with 2-methyl isophthalic acid-phenyl propylene, purity 95%.
The normal hexane recrystallization gets the 5g title product, purity 99%.
Embodiment 2
In the reaction flask of clean dried, drop into 6.8ml methylene dichloride, 7g aluminum chloride, stir and cool to-3 ℃, drip 6 gram alpha-chloro propionyl chlorides, drip off, kept this thermotonus 20 minutes;-2 ℃, nitrogen protection, Dropwise 5 gram 2-methyl isophthalic acid-phenyl propylene drips off, and keeps this thermotonus 1 hour.Reaction solution is added the reaction that is hydrolyzed in the frozen water, and hydrolysis temperature is controlled at 8 ℃.Hydrolyzed solution leaves standstill, separatory.Water layer is with 10ml dichloromethane extraction one time.The dichloromethane extract and the bed of material merge, with water washing 3 times, and each water 16ml.Reclaim methylene dichloride, get blackish green 8 gram 1-[4-(2-methyl isophthalic acid-propenyl) phenyl]-2-chloro-1-acetone, yield 97%, gc is surveyed content greater than 95%.
In reaction flask, add 6 gram NSC 6366s, 20ml toluene, nitrogen replacement is warming up to 60 ℃ and adds 1 gram tosic acid, 8 gram 1-[4-(2-methyl isophthalic acid-propenyl) phenyl]-2-chloro-1-acetone, and 110 ℃ of band water reactions that reflux are to clarification.
Steam toluene to 120 ℃, add 0.2 gram zinc oxide, continue to be warming up to 155 ℃ of reactions 1 hour.
Cool to 70 ℃, add 4ml 30%NaOH, keep 85 ℃ of reactions 2 hours, reduce to room temperature, left standstill 1 hour, inhale and remove the upper strata mother liquor; Add 20ml water dissolution solid, add the 10ml*3 methylbenzene extraction, divide and remove toluene layer.
Water layer, filters to PH5～6 with 30% hcl acidifying, obtains 6 gram 2-[4-(2-methyl isophthalic acid-propenyl) phenyl] propionic acid, collects rate 77% with 2-methyl isophthalic acid-phenyl propylene, purity 95.1%.
The normal hexane recrystallization gets the 5g title product, purity 99.2%.
Embodiment 3
In the reaction flask of clean dried, drop into 6.8ml methylene dichloride, 7g aluminum chloride, stir and cool to-1 ℃, drip 6 gram alpha-chloro propionyl chlorides, drip off, kept this thermotonus 20 minutes; 0 ℃, nitrogen protection, Dropwise 5 gram 2-methyl isophthalic acid-phenyl propylene drips off, and keeps this thermotonus 1 hour.Reaction solution is added the reaction that is hydrolyzed in the frozen water, and hydrolysis temperature is controlled at 9 ℃.Hydrolyzed solution leaves standstill, separatory.Water layer is with 10ml dichloromethane extraction one time.The dichloromethane extract and the bed of material merge, with water washing 3 times, and each water 16ml.Reclaim methylene dichloride, get blackish green 8 gram 1-[4-(2-methyl isophthalic acid-propenyl) phenyl]-2-chloro-1-acetone, yield 97%, gc is surveyed content greater than 95%.
In reaction flask, add 6 gram NSC 6366s, 20ml toluene, nitrogen replacement is warming up to 55 ℃ and adds 1 gram tosic acid, 8 gram 1-[4-(2-methyl isophthalic acid-propenyl) phenyl]-2-chloro-1-acetone, and 105 ℃ of band water reactions that reflux are to clarification.
Steam toluene to 115 ℃, add 0.2 gram zinc oxide, continue to be warming up to 160 ℃ of reactions 1 hour.
Cool to 70 ℃, add 4ml 30%NaOH, keep 80 ℃ of reactions 2 hours, reduce to room temperature, left standstill 1 hour, inhale and remove the upper strata mother liquor; Add 20ml water dissolution solid, add the 10ml*3 methylbenzene extraction, divide and remove toluene layer.
Water layer, filters to PH5～6 with 30% hcl acidifying, obtains 6 gram 2-[4-(2-methyl isophthalic acid-propenyl) phenyl] propionic acid, collects rate 77% with 2-methyl isophthalic acid-phenyl propylene, purity 95%.
The normal hexane recrystallization gets the 5g title product, purity 99.1%.
Claims (6)
1. the preparation method of a 2-[4-(2-methyl isophthalic acid-propenyl) phenyl] propionic acid is characterized in that 2-methyl isophthalic acid-phenyl propylene and alpha-chloro propionyl chloride with the NSC 6366 condensation reaction, making through rearrangement, hydrolysis, acidifying through friedel-crafts reaction again.
2. preparation method according to claim 1; It is characterized in that said friedel-crafts reaction is: aluminum chloride is dissolved in the methylene dichloride, drips the alpha-chloro propionyl chloride in-5～0 ℃ and react, reaction finishes; Dripping 2-methyl isophthalic acid-phenyl propylene in-5～0 ℃ again reacts; Reaction finishes posthydrolysis, through dichloromethane extraction, washing, makes 1-[4-(2-methyl isophthalic acid-propenyl) phenyl]-2-chloro-1-acetone.
3. preparation method according to claim 1; It is characterized in that said condensation reaction is: in the NSC 6366 toluene solution; Add tosic acid, 1-[4-(2-methyl isophthalic acid-propenyl) phenyl]-2-chloro-1-acetone, 100～115 ℃ of band water reactions that reflux make 2-(2-chloropropyl)-2-[4-(2-methyl isophthalic acid-propenyl) phenyl]-5; 5-dimethyl--1, the toluene solution of 3-dioxane.
4. preparation method according to claim 1; It is characterized in that said rearrangement reaction is: with 2-(2-chloropropyl)-2-[4-(2-methyl isophthalic acid-propenyl) phenyl]-5,5-dimethyl--1, the toluene solution of 3-dioxane steam toluene to 115～120 ℃; Add zinc oxide; Be warming up to 140～160 ℃ and carry out rearrangement reaction, make the toluene solution of (2,2-dimethyl--3-chlorine) propyl group-2-[4-(2-methyl isophthalic acid-propenyl) phenyl] propionic ester.
5. preparation method according to claim 1; It is characterized in that said hydrolysis reaction is: the toluene solution of (2,2-dimethyl--3-chlorine) propyl group-2-[4-(2-methyl isophthalic acid-propenyl) phenyl] propionic ester is cooled to 65 ~ 75 ℃, adds NaOH; 70～85 ℃ are hydrolyzed; The hydrolysis Hou Jiashui that finishes adds methylbenzene extraction again, makes 2-[4-(2-methyl isophthalic acid-propenyl) phenyl] the Sodium Propionate aqueous solution.
6. preparation method according to claim 1 is characterized in that said acidification reaction is: 2-[4-(2-methyl isophthalic acid-propenyl) phenyl] the Sodium Propionate aqueous solution gets 2-[4-(2-methyl isophthalic acid-propenyl) phenyl] propionic acid with hcl acidifying.
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|---|---|---|---|
| CN2012101957548A CN102701949A (en) | 2012-06-14 | 2012-06-14 | Method for preparing 2-[4-(2-methyl-1-propenyl)phenyl]propionic acid |
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| CN2012101957548A CN102701949A (en) | 2012-06-14 | 2012-06-14 | Method for preparing 2-[4-(2-methyl-1-propenyl)phenyl]propionic acid |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1082022A (en) * | 1992-08-14 | 1994-02-16 | 山东新华制药厂 | Molecular transposition prepares the technology of Ibuprofen BP/EP under the catalysis |
| WO2011051375A1 (en) * | 2009-10-28 | 2011-05-05 | Dompé S.p.A. | 2-aryl-propionamide derivatives useful as bradykinin receptor antagonists and pharmaceutical compositions containing them |
-
2012
- 2012-06-14 CN CN2012101957548A patent/CN102701949A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1082022A (en) * | 1992-08-14 | 1994-02-16 | 山东新华制药厂 | Molecular transposition prepares the technology of Ibuprofen BP/EP under the catalysis |
| WO2011051375A1 (en) * | 2009-10-28 | 2011-05-05 | Dompé S.p.A. | 2-aryl-propionamide derivatives useful as bradykinin receptor antagonists and pharmaceutical compositions containing them |
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