IE65258B1 - New process for producing a phenyl propionic derivative - Google Patents
New process for producing a phenyl propionic derivativeInfo
- Publication number
- IE65258B1 IE65258B1 IE16490A IE16490A IE65258B1 IE 65258 B1 IE65258 B1 IE 65258B1 IE 16490 A IE16490 A IE 16490A IE 16490 A IE16490 A IE 16490A IE 65258 B1 IE65258 B1 IE 65258B1
- Authority
- IE
- Ireland
- Prior art keywords
- process according
- aminophenyl
- radical
- propionic acid
- propionic
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 title description 2
- -1 C1-C6 alkyl radical Chemical group 0.000 claims abstract description 24
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 12
- 239000003444 phase transfer catalyst Substances 0.000 claims abstract description 9
- YPGCWEMNNLXISK-UHFFFAOYSA-N hydratropic acid Chemical class OC(=O)C(C)C1=CC=CC=C1 YPGCWEMNNLXISK-UHFFFAOYSA-N 0.000 claims abstract description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 4
- 239000001257 hydrogen Substances 0.000 claims abstract description 4
- 239000012736 aqueous medium Substances 0.000 claims abstract description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 24
- 235000019260 propionic acid Nutrition 0.000 claims description 13
- WOMVICAMAQURRN-UHFFFAOYSA-N 2-(4-aminophenyl)propanoic acid Chemical compound OC(=O)C(C)C1=CC=C(N)C=C1 WOMVICAMAQURRN-UHFFFAOYSA-N 0.000 claims description 12
- 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 12
- 238000005804 alkylation reaction Methods 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 230000029936 alkylation Effects 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 150000004714 phosphonium salts Chemical class 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims description 2
- 150000003254 radicals Chemical class 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims 1
- 230000002209 hydrophobic effect Effects 0.000 claims 1
- 239000007788 liquid Substances 0.000 claims 1
- QLPMKRZYJPNIRP-UHFFFAOYSA-M methyl(trioctyl)azanium;bromide Chemical group [Br-].CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC QLPMKRZYJPNIRP-UHFFFAOYSA-M 0.000 claims 1
- 239000012454 non-polar solvent Substances 0.000 claims 1
- 239000012429 reaction media Substances 0.000 claims 1
- 239000002253 acid Substances 0.000 abstract description 8
- 230000015572 biosynthetic process Effects 0.000 abstract description 7
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 150000007513 acids Chemical class 0.000 abstract 1
- 229940100198 alkylating agent Drugs 0.000 abstract 1
- 239000002168 alkylating agent Substances 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 abstract 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 125000005907 alkyl ester group Chemical group 0.000 description 4
- 150000001412 amines Chemical group 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 3
- XKBGEWXEAPTVCK-UHFFFAOYSA-M methyltrioctylammonium chloride Chemical compound [Cl-].CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC XKBGEWXEAPTVCK-UHFFFAOYSA-M 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000001308 synthesis method Methods 0.000 description 3
- OHXAOPZTJOUYKM-UHFFFAOYSA-N 3-Chloro-2-methylpropene Chemical compound CC(=C)CCl OHXAOPZTJOUYKM-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- VJGNLOIQCWLBJR-UHFFFAOYSA-M benzyl(tributyl)azanium;chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CC1=CC=CC=C1 VJGNLOIQCWLBJR-UHFFFAOYSA-M 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- LSEFCHWGJNHZNT-UHFFFAOYSA-M methyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 LSEFCHWGJNHZNT-UHFFFAOYSA-M 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 235000011121 sodium hydroxide Nutrition 0.000 description 2
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 2
- MQAYPFVXSPHGJM-UHFFFAOYSA-M trimethyl(phenyl)azanium;chloride Chemical compound [Cl-].C[N+](C)(C)C1=CC=CC=C1 MQAYPFVXSPHGJM-UHFFFAOYSA-M 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- USEGQJLHQSTGHW-UHFFFAOYSA-N 3-bromo-2-methylprop-1-ene Chemical compound CC(=C)CBr USEGQJLHQSTGHW-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 125000005394 methallyl group Chemical group 0.000 description 1
- JSQLPIGKVBUMBF-UHFFFAOYSA-N methyl 2-(4-aminophenyl)propanoate Chemical compound COC(=O)C(C)C1=CC=C(N)C=C1 JSQLPIGKVBUMBF-UHFFFAOYSA-N 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 150000004672 propanoic acids Chemical class 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 238000010517 secondary reaction Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 150000003613 toluenes Chemical class 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/18—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/52—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
- C07C229/54—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C229/56—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring with amino and carboxyl groups bound in ortho-position
- C07C229/58—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring with amino and carboxyl groups bound in ortho-position having the nitrogen atom of at least one of the amino groups further bound to a carbon atom of a six-membered aromatic ring, e.g. N-phenyl-anthranilic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Hydrogenated Pyridines (AREA)
Abstract
The invention relates to the field of organic chemistry, and more specifically to the synthesis of phenylpropionic acids. Its specific subject is a new process for the preparation of 2-[4-(R-amino)phenyl]propionic acids of general formula I <IMAGE> which consists in subjecting a 2-(4-aminophenyl)propionic derivative of formula II <IMAGE> in which R1 is hydrogen or a C1-C6 alkyl radical, to the action of an alkylating agent in a heterogeneous phase in the presence of a phase transfer catalyst and a basic agent in an aqueous medium. The acids obtained are active principles of medicaments.
Description
Description The present invention relates to the obtaining of a 2phenyl propionic acid by a new process.
A more particular subject of the invention is the obtaining of 2-phenyl propionic acid the phenyl nucleus of which is substituted by an amino acid.
A specific subject of the invention is a new process for the synthesis of 2(R-aminophenyl) propionic acids and, in particular, of 2-(4-methallylaminophenyl) propionic acid. In fact, the literature, such as for example the US Patent 3,957,850 has shown the difficulty of carrying out the alkylation of the amine function carried by such phenylpropionic acids. Now, it has turned out that the selective mono-alkylation of these 2-(4-aminophenyl) propionic acids is important insofar as it leads to a significant increase in the pharmacological activity and/or a reduction in the degree of toxicity.
On the other hand, the NN-disubstituted derivatives are, in general, significantly less active and may, therefore, constitute an additional load the elimination of which is often difficult and leads to significant losses in the yield in the final stages of the synthesis.
This is why finding a new synthesis method which produces only a limited formation of dialkylated derivatives with nitrogen or which permits their separation in much easier conditions has proved important.
This problem was able to be resolved according to the invention by a process which consists of subjecting a 2(4aminophenyl) propionic derivative of formula II: COOR; (II) in which Ri is an alkyl radical having 1 to 6 carbon atoms or hydrogen in solution in an inert organic water-immiscible and non2 polar solvent, to the action of an alkylation agent in heterogeneous phase, in the presence of a phase transfer catalyst and a basic agent in aqueous medium, in order to obtain a 2-(4-R aminophenyl) propionic acid of general formula I: RHN COOH (I) in which R is a lower alkyl radical, optionally substituted by a hydroxyl, a lower alkenyl radical having 2 to 6 carbon atoms, a lower alkynyl radical having 2 to 4 carbon atoms, a lower aralkyl radical.
In a preferred manner, the R radical is a methallyl. It can also be an alkenyl radical such as allyl, an aralkyl radical such as benzyl, a substituted alkyl radical such as beta-hydroxyethyl.
The phase transfer catalyst is a quaternary ammonium salt or a phosphonium salt, soluble in both types of solvents. Methyltrioctyl ammonium chloride is preferably used, marketed under the name ALIQUAT 336, as well as other ammonium or phosphonium salts, such as methyl triphenyl phosphonium bromide, trimethyl phenyl ammonium chloride, tetrabutyl ammonium bromide and benzyl tributyl ammonium chloride.
The quantity of catalyst used is about 10 g per mole of 2-(4-aminophenyl) propionic acid or its alkyl ester used. The concentration of 2-(4-aminophenyl) propionic acid or of the ester of this acid is about one mole per 400 ml of waterimmiscible organic solvent.
The concentration of alkylation agent which is preferably a methallyl halide, such as methallyl chloride or methallyl bromide, is 1 to 1.4 mole per mole of 2-(4aminophenyl) propionic acid or of the alkyl ester of this acid. 1.1 to 1.4 mole of methallylation agent is preferably used per mole of 2-(4-aminophenyl) propionic acid or of one of its alkyl esters.
The 2-(4-methallylaminophenyl) propionic acid formed in this reaction remains in the organic phase because the quantity of basic agent is almost that of the stoichiometry and this explains why the product recovered is directly 2-(4methallylaminophenyl) propionic acid itself and not one of its salts. Under these conditions, there is no salification reaction and isolation of the acid is made easier.
The basic agent capable of fixing the hydrogen acid or the anion formed during the alkylation reaction is a strong base, preferably an alkali metal hydroxide such as sodium hydroxide. The concentration used is preferably 1 to 1.1 mole of base per 1 mole of acid or ester of 2-(4-aminophenyl) propionic acid, dissolved in water at a concentration of the order of 10%.
The reaction is carried out at a temperature below that of the boiling point of the organic solvent and, preferably, between 80 and 85°. It is preferable to operate under an inert atmosphere, such as for example by bubbling through nitrogen.
The duration of the reaction is at least two hours. No advantage is gained and a better yield is not obtained when the reaction is continued for longer than 4 hours.
After the reaction, the supernatant organic phase is separated off and washed with water. The organic phase is extracted with about 1N soda. It is then acidified to pH 1 with 1N hydrochloric acid. The by-products (in particular dialkylated derivatives) are insoluble in this solution and are eliminated by extraction with an organic solvent.
This acid solution is treated with activated charcoal, filtered and brought to pH 3 by the addition of soda or an alkali metal salt of a weak acid. r The 2-(4-alkylaminophenyl) propionic acid which crystallizes is separated out by filtration. It is washed with water and dried.
It was noted with interest that when an alkyl ester of 2-(4-aminophenyl) propionic acid is used at the start, the alkylation reaction carried out under these conditions is accompanied by the saponification of the ester function so that the product obtained is directly propionic acid.
The 2-(4-methallylaminophenyl) obtained is a known product (B.
Therapeutique 14 (1979) p inflammatory properties publications.
However, the production of 2-(4-methallylaminophenyl) propionic acid had up to now been held up because the synthesis methods were all hindered by a stage which was difficult to achieve: alkylation of the amino derivative by a methallyl halide. This stage consists of subjecting, beforehand or not, the amino derivative to the action of a methallylation agent and it had proved up to now impossible to avoid the simultaneous formation of a mono methallylamino derivative and of a dimethallyl amino derivative. It was noted, in particular, that a labile partial blocking of the amine function which could have avoided this secondary reaction was quickly inoperative because it was difficult to eliminate subsequently. Therefore, the different synthesis methods lead inescapably to the formation of this by-product, with no therapeutic use, and the elimination of which required an additional stage and a significant reduction in the overall yield of the synthesis.
The following examples illustrate the invention. 2-(4-alkylaminophenyl) propionic acid thus DUMAITRE cf Chimie 207-214) whose analgesic and antiare the subject of numerous Example 1 Place: - 165 g (1 mole) of 2-(4-aminophenyl) propionic acid - 400 cm3 of toluene - 100 g of methallyl chloride (1.1 mole) - 10 g of Aliquat 336 - 250 cm3 of water - 92.5 cm3 of 32% soda lye (1 mole) in a reaction vessel provided with good agitation, a condenser, a thermometer and a nitrogen supply.
Heat the mixture for 3 hours at 85°.
Decant, wash the toluene solution twice with water.
Extract this toluene phase with 1 litre of 1N soda. Pour the alkaline solution into 1.5 litres of 1N hydrochloric acid (pH = 0.8). Extract three times with toluene. Add charcoal (filter). Bring the pH to 3 by the slow addition of 1N soda under vigorous agitation. Separate off the precipitate formed, wash it with water and dry it.
In this way 140 g (yield = 64%) of creamy white crystals are isolated. M.p. = approx. 107°.
Example 2 In an identical manner to that of Example 1, 135 g of 2(4-methallylaminophenyl) propionic acid is obtained starting with 179 g of methyl 2-(4-aminophenyl) propionate, using Aliguat 336.
Examples 3 to 7 In an identical manner to that of Example methallylaminophenyl) propionic acid is obtained with 2-(4-aminophenyl) propionic acid using the phase transfer catalysts: 1, 2-(4starting following Example Catalyst used Yield 20 3 T Ε B A 57% 4 Methyl triphenyl phosphonium bromide 58% 5 Phenyl trimethyl ammonium chloride 57.5% 6 Tetrabutyl ammonium bromide 58.5% 7 Benzyl tributyl ammonium chloride 62%
Claims (2)
1.Claims : 1) A process for obtaining 2-phenyl propionic acids substituted by an amino radical, characterized in that a 2(4-aminophenyl) propionic derivative of formula II: CH, I ’ CH- COOR, (II) in which R-| is an alkyl radical having 1 to 6 carbon atoms or hydrogen in solution in an inert organic, water-immiscible and nonpolar solvent, is subjected to the action of an alkylation 10 agent in heterogeneous phase, in the presence of a phase transfer catalyst and a basic agent in aqueous medium in order to obtain a 2-(4-R aminophenyl) propionic acid of general formula I: 15 in which R is a lower alkyl radical optionally substituted by a hydroxyl, a lower alkenyl radical, a lower alkynyl radical or a lower aralkyl radical.
2. ) A process according to claim 1 in which the R radical is the methallyl radical. 2Q 3) A process according to claim 1 in which the waterimmiscible organic solvent is a liquid aromatic hydrocarbon. 4) A process according to claim 1 in which the phase transfer catalyst . is a quaternary ammonium salt soluble in both the hydrophobic solvents and in water. 7 25 5) A process according to claim 1 in which the phase transfer catalyst is a triphenylalkyl phosphonium salt. 6) A process according to claim 4 in which the phase transfer catalyst is methyltrioctyl ammonium bromide. Ί Ί) A process according to one of claims 1 to 6 in which the quantity of phase transfer catalyst introduced into the reaction medium is of the order of 10 g per mole of 2-(4aminophenyl) propionic acid. 5 8) A process according to one of claims 1 to 7 in which the concentration of 2-(4-aminophenyl) propionic derivative is about 1 mole per 400 ml of water-immiscible organic solvent. 9) A process according to one of claims 1 to 8 in which the concentration of alkylation agent is comprised between 1 and 10 1.4 mole per mole of 2-(4-aminophenyl) propionic acid. 10) A process according to claim 9 in which the concentration of methallylation agent varies from 1 .1 to 1.4 mole per mole of 2-(4-aminophenyl) propionic acid. 11) A process substantially as hereinbefore described with 15 reference to the Examples. 12) A 2-(4-alkylamino phenyl)propionic acid of general formula I according to claim 1, whenever prepared or obtained in the process of claims 1 to 11.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8900522A FR2642752B1 (en) | 1989-01-16 | 1989-01-16 | NEW PROCESS FOR OBTAINING A PROPIONIC PHENYL ACID |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE900164L IE900164L (en) | 1990-07-16 |
| IE65258B1 true IE65258B1 (en) | 1995-10-18 |
Family
ID=9377804
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE16490A IE65258B1 (en) | 1989-01-16 | 1990-01-16 | New process for producing a phenyl propionic derivative |
Country Status (12)
| Country | Link |
|---|---|
| EP (1) | EP0379423B1 (en) |
| JP (1) | JP2852393B2 (en) |
| KR (1) | KR0177151B1 (en) |
| CN (1) | CN1042330C (en) |
| AT (1) | ATE90934T1 (en) |
| DE (1) | DE69002011T2 (en) |
| DK (1) | DK0379423T3 (en) |
| ES (1) | ES2058828T3 (en) |
| FI (1) | FI101960B (en) |
| FR (1) | FR2642752B1 (en) |
| IE (1) | IE65258B1 (en) |
| PT (1) | PT92873B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102206150A (en) * | 2011-04-11 | 2011-10-05 | 启东东岳药业有限公司 | Method for purifying 2-phenylpropionic acid |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH525882A (en) * | 1967-07-22 | 1972-07-31 | Merck Patent Gmbh | (I) A=CO2A1, CONA2A3, CONA4, C(=NOH)OH, or C(OR9)3 A1-A3=H, (1-12C) alkyl or cycloalkyl opt. contng. OH, NH2 and/or 1-2 multiple bonds, and opt. broken by |
| DE1913742A1 (en) * | 1968-03-27 | 1969-10-09 | Ciba Geigy | Tertiary aliphatic amino acids |
| FR2137211B1 (en) | 1971-05-17 | 1974-08-02 | Bouchara Emile | |
| FR2193579A2 (en) * | 1972-07-25 | 1974-02-22 | Bouchara Emile | Para amino phenyl acetic acids - analgesics and antiinflammatories, prepd. by alkylation of prim amino acid |
-
1989
- 1989-01-16 FR FR8900522A patent/FR2642752B1/en not_active Expired - Fee Related
-
1990
- 1990-01-15 FI FI900226A patent/FI101960B/en not_active IP Right Cessation
- 1990-01-16 DK DK90400120.3T patent/DK0379423T3/en active
- 1990-01-16 ES ES90400120T patent/ES2058828T3/en not_active Expired - Lifetime
- 1990-01-16 AT AT90400120T patent/ATE90934T1/en not_active IP Right Cessation
- 1990-01-16 KR KR1019900000526A patent/KR0177151B1/en not_active Expired - Fee Related
- 1990-01-16 IE IE16490A patent/IE65258B1/en not_active IP Right Cessation
- 1990-01-16 JP JP2007016A patent/JP2852393B2/en not_active Expired - Lifetime
- 1990-01-16 PT PT92873A patent/PT92873B/en not_active IP Right Cessation
- 1990-01-16 EP EP90400120A patent/EP0379423B1/en not_active Expired - Lifetime
- 1990-01-16 DE DE90400120T patent/DE69002011T2/en not_active Expired - Fee Related
- 1990-07-16 CN CN90106801A patent/CN1042330C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| PT92873B (en) | 1995-12-29 |
| FI900226A0 (en) | 1990-01-15 |
| EP0379423B1 (en) | 1993-06-23 |
| KR0177151B1 (en) | 1999-04-15 |
| FR2642752B1 (en) | 1991-04-12 |
| KR900011712A (en) | 1990-08-02 |
| FR2642752A1 (en) | 1990-08-10 |
| FI101960B1 (en) | 1998-09-30 |
| FI101960B (en) | 1998-09-30 |
| DE69002011T2 (en) | 1993-12-23 |
| JP2852393B2 (en) | 1999-02-03 |
| ATE90934T1 (en) | 1993-07-15 |
| CN1042330C (en) | 1999-03-03 |
| CN1058206A (en) | 1992-01-29 |
| DE69002011D1 (en) | 1993-07-29 |
| PT92873A (en) | 1990-07-31 |
| ES2058828T3 (en) | 1994-11-01 |
| EP0379423A1 (en) | 1990-07-25 |
| JPH02262547A (en) | 1990-10-25 |
| IE900164L (en) | 1990-07-16 |
| DK0379423T3 (en) | 1993-11-15 |
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