CN100548969C - A kind of preparation method of o-chlorobenzene glycine - Google Patents
A kind of preparation method of o-chlorobenzene glycine Download PDFInfo
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Abstract
The present invention relates to a kind of preparation method of clopidogrel intermediate o-chlorobenzene glycine, this method may further comprise the steps: the A. cyaniding; B. basic hydrolysis, decolouring; C. neutralization, crystallization; D. suction filtration, oven dry.Simple to operate, the safety of the preparation method of o-chlorobenzene glycine of the present invention, with short production cycle, cost is low, is fit to the suitability for industrialized production of extensiveization; Avoided the generation of hypertoxic gas cyaniding hydrogen, safety and reliability; Reduce the production of the coal-tar middle oil shape thing of cyaniding process, guaranteed the quality of product; Reduced the consumption of methyl alcohol and ammoniacal liquor, less environmental protection pressure; The o-chlorobenzene glycine yield that utilizes method of the present invention preparation is up to (in o-chlorobenzaldehyde) more than 65%, and product is the crystalline powder of white or off-white color.
Description
Technical field
The present invention relates to a kind of preparation method of medicine intermediate, relate in particular to the preparation method of clopidogrel intermediate o-chlorobenzene glycine, belong to field of medicine and chemical technology.
Background technology
Clopidogrel (clopidogrel), its chemical name is (+)-2-(2-chloro-phenyl-)-2-(4,5,6,7-tetramethylene sulfide [3,2-c] and pyridine-5) methyl acetate, clopidogrel is a kind of active drug for the treatment of atherosclerosis, cerebrovascular disease and apoplexy, suppress platelet activation by suppressing the ADP approach, thus anticoagulant.O-chlorobenzene glycine is the important intermediate of synthetic clopidogrel, and its preparation method bibliographical information is more, and the method for existing synthetic o-chlorobenzene glycine is to be main raw material with the o-chlorobenzaldehyde, through cyaniding, and hydrolysis, neutralization obtains target product.
(" study on the synthesis of dl-o-chlorobenzene glycine " such as the Ma Yuzhuo of Guangdong Pharmaceutical University, Mei Wenjie, article numbering 1006-8783 (2006) 03-0239-02) having introduced with the o-chlorobenzaldehyde is main raw material, in the presence of ammonium chloride or volatile salt, carry out cyaniding through sodium cyanide solution, cyaniding finishes back benzene and extracts, perhaps stirring reaction 7 days at room temperature, again by in hydrochloric acid hydrolysis and the ammoniacal liquor and the preparation o-chlorobenzene glycine, yield is 43.5%-50%; Method according to the document prepares the o-chlorobenzene glycine long reaction time; yield is lower; solvent, ammoniacal liquor consumption are big; the environmental protection meeting is caused certain pressure; and directly utilize the acidic solution hydrolysis behind the cyanogenation, and the hydrogen ion in cyano group and the acid is in conjunction with the hydrocyanic acid gas that generates severe toxicity, and it is very high to handle the required safety cost of these hypertoxic gases; therefore the preparation method that relates to of the document can only carry out small-scale test, and can't realize large-scale industrial production.
Summary of the invention
Defectives such as preparation method's long reaction time, the yield that the present invention is directed to existing o-chlorobenzene glycine is low, safety cost is high, environmental pollution is heavier, provide a kind of simple to operate, cost is low, the high preparation method who is fit to the o-chlorobenzene glycine of suitability for industrialized production of yield.
The present invention is also long at the method process cycle of existing preparation o-chlorobenzene glycine, does not reach the defective that suitability for industrialized production requires, and provides a kind of with short production cycle, can reach the preparation method of the o-chlorobenzene glycine of suitability for industrialized production requirement.
Above-mentioned technical problem of the present invention is implemented by the following technical programs: a kind of preparation method of o-chlorobenzene glycine, and this method may further comprise the steps:
A, cyaniding: get methyl alcohol and supercarbonate and join in the reactor, add cyanide salt solution and ammoniacal liquor then and then add under the condition that is warming up to 50 ℃～100 ℃ o-chlorobenzaldehyde earlier reacts 4～6 hours under temperature is 30 ℃～50 ℃ condition after and reacted 4～7 hours, the reaction back concentrates and obtains the cyaniding concentrated solution;
B, basic hydrolysis, decolouring: the cyaniding concentrated solution after above-mentioned concentrate was stirred 0.5～2 hour being warming up under the highly basic condition of pH value 〉=12 under 90 ℃～120 ℃ the condition; Be warming up to 120 ℃～170 ℃ then, control pressure is basic hydrolysis 3～8 hours under the condition of 0.2Mpa～0.6Mpa, and the hydrolysis rear decoloring obtains hydrolysate;
C, neutralization, crystallization: the hydrolysate of said hydrolyzed decolouring is neutralized to pH value 8～10 o'clock crystallization by acid under 50 ℃～70 ℃ condition, growing the grain 10～30 minutes continues to be neutralized to pH value 5.0～6.5 by acid and obtains the o-chlorobenzene glycine crystal;
D, suction filtration, oven dry: is 25 ℃～35 ℃ suction filtrations with the above-mentioned o-chlorobenzene glycine crystal that obtains in temperature, and solid obtains o-chlorobenzene glycine after by vacuum drying behind the suction filtration.
Cyanogenation in preparation method's steps A of the present invention adopts the operation that heats up behind the first low temperature to reduce the production at the coal-tar middle oil shape thing of cyaniding process, makes aftertreatment easier; It is to heat up after 4-6 hour in 30-50 ℃ of reaction that cyanogenation begins, if be lower than intensification in 4 hours, then sodium cyanide concentration is higher in the system, causes the generation of tarry materials; If be higher than intensification in 6 hours, then prolong the reaction times, increase reaction cost; Be warming up to 50-100 ℃, if the temperature that raises is lower than 50 ℃, then speed of reaction is slow, and long reaction time if the temperature that raises is higher than 100 ℃, then generates tarry materials easily, consumes more thermal energy simultaneously.Intensification afterreaction 4-7 hour, if be lower than 4 hours, then conversion of raw material is lower, if be higher than 7 hours, then impels the generation of by product, increases energy consumption simultaneously.
In the preparation method of above-mentioned o-chlorobenzene glycine, the supercarbonate described in the steps A is a kind of in bicarbonate of ammonia, sodium bicarbonate, the saleratus; Described cyanide salt solution is sodium cyanide, and its concentration is 20%～50%, and wherein the mol ratio of each reaction mass is an o-chlorobenzaldehyde: methyl alcohol: supercarbonate: cyanide salt: ammoniacal liquor is 1: 3～7: 1～3: 1～5: 1～5.Higher according to this mol ratio o-chlorobenzaldehyde transformation efficiency, production cost is low, the yield height.
In the preparation method of above-mentioned o-chlorobenzene glycine, stirred 8～15 minutes after in cyanide salt solution, adding ammoniacal liquor in the steps A, add o-chlorobenzaldehyde again and carry out cyanogenation under stirring condition, wherein adding the time of stirring behind the o-chlorobenzaldehyde is 15～30 minutes.Add the purpose that stirs behind the ammoniacal liquor and be in order to prevent the hydrolysis of cyanide salt, add purpose that o-chlorobenzaldehyde stirs again and be and avoid the o-chlorobenzaldehyde partial concn too high and make the reaction aggravation, thereby cause the cyanogenation system temperature to raise, the hydrolysis of part cyanide salt.
In the preparation method of above-mentioned chlorobenzene glycine, the thickening temperature described in the steps A is 50 ℃～100 ℃, and concentrated pressure is normal pressure.Cyanogenation finishes back normal pressure concentration of reaction solution removing methyl alcohol as much as possible, thereby guarantees after follow-up macromolecule alkali for hydrolysis, neutralization reaction are finished, and reduces the dissolving of product in solution in the cooling crystallization process, improves yield.
Adopting among preparation method's step B of o-chlorobenzene glycine of the present invention pressurizes under the highly basic condition of pH value 〉=12 is hydrolyzed, wherein being warming up to earlier and stirring 0.5～2 hour under 90 ℃～120 ℃ the condition is for ammonia residual in the system of driving away, because ammonia is the by product of hydrolysis reaction, if do not drive ammonia residual in the embodiment away, not only can influence the speed of hydrolysis reaction, and can influence the yield of product; Pressure is 0.2MPa～0.6MPa in the basic hydrolysis, if pressure is lower than 0.2MPa, then prolongs hydrolysis time; If basic hydrolysis pressure is higher than 0.6MPa, then there is by product to generate, simultaneously equipment there is higher requirement.Hydrolysis time is 3～8 hours, if be lower than 3 hours, then hydrolysis is incomplete; If be higher than 8 hours, then cause the generation of by product, increase energy consumption simultaneously.Hydrolysising reacting temperature is controlled at 120-170 ℃, if be lower than 120 ℃, then the hydrolysis of cyaniding product is incomplete, if be higher than 170 ℃, then cause the increase of by product, increase energy consumption simultaneously, as preferably, the temperature of basic hydrolysis is 130 ℃～150 ℃ among the step B, and the basic hydrolysis time is 4～6 hours.Residual cyano group is hydrolyzed to ammonia and carbonate in the cyanating solution simultaneously, makes next step neutralization reaction operation safer.The used alkali of basic hydrolysis is alkali metal hydroxide or alkaline earth metal hydroxides such as sodium hydroxide, potassium hydroxide etc., and as preferably, the alkali in the basic hydrolysis step is selected sodium hydroxide for use.
In the preparation method of above-mentioned o-chlorobenzene glycine, it is to stir 0.5～2 hour under 90 ℃～120 ℃ the condition in temperature that the hydrolysis of step B neutral and alkali finishes the back, be cooled to then under 70 ℃～90 ℃ the condition with behind the activated carbon decolorizing hydrolysate.Alkaline hydrolysis is once caught up with ammonia after finishing again, and purpose is to prevent that ammonia residual in the reaction solution from generating ammonium salt in the reaction of N-process neutralizing acid, thereby influences neutralization reaction.
Preparation method's step C of the present invention neutralizes at 50～70 ℃ with acid, if neutral temperature is lower than 50 ℃, then has solid salt and separate out in N-process, if be higher than 70 ℃, then deepens the color of product, thereby influences the quality of product.When having crystal to separate out growing the grain 10-30 minute, the purpose of growing the grain was to prevent that product from separating out in a large number, makes product have good crystal formation simultaneously.Be neutralized to PH5.0～6.5 at last,, then have o-chlorobenzene glycine salt residual in the solution, reduce the yield of o-chlorobenzene glycine if PH is higher than 6.5; If PH is lower than 5.0, then can increase the solubleness of product in solution, thereby reduce yield, increase the consumption of acid, thereby increase the cost of subsequent disposal.Acid used in the described neutralization reaction is hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid, a kind of in the Hydrogen bromide; As preferably, used acid is hydrochloric acid in the neutralization reaction.
Among the step D of the present invention and after solution be cooled to 20 ℃ of-35 ℃ of suction filtrations, if the suction filtration temperature is higher than 35 ℃, then product is not separated out fully, influences yield, if the suction filtration temperature is lower than 20 ℃, then a large amount of inorganic salt are separated out simultaneously and are caused filter cake to still have more salt to exist after washing once.
In the preparation method of above-mentioned o-chlorobenzene glycine, the solid among the step D behind the suction filtration carries out vacuum drying by washing, methyl alcohol after washing.Filter cake behind the suction filtration washes with water, removes the inorganic salt of carrying secretly in the filter cake, and methyl alcohol is washed, and removes the by product that generates in the dereaction.
In the preparation method of above-mentioned o-chlorobenzene glycine, the temperature of the described vacuum drying of step D is 70 ℃～90 ℃, and drying time is 6～10 hours; Described vacuum tightness is 0.05Mpa～0.09Mpa.If temperature is lower than 70 ℃, then prolong time of drying, if temperature is higher than 90 ℃, then product color in drying process requirement of not reaching white or off-white color; If drying time is lower than 6 hours, then product drying is incomplete, if drying time is higher than 10 hours, then influences the color of product, increases energy consumption, prolongs single batch of production cycle.The vacuum tightness of vacuum drying is 0.05-0.09MPa, if vacuum tightness is lower than 0.05MPa, then prolongs drying time, if vacuum tightness is higher than 0.09MPa, then drying plant is had higher requirement.
In sum, the preparation method of o-chlorobenzene glycine of the present invention has the following advantages:
Simple to operate, the safety of the preparation method of o-chlorobenzene glycine of the present invention, with short production cycle, cost is low, is fit to the suitability for industrialized production of extensiveization;
The preparation method of o-chlorobenzene glycine of the present invention has avoided the generation of hypertoxic gas cyaniding hydrogen, safety and reliability; Reduce the production of the coal-tar middle oil shape thing of cyaniding process, guaranteed the quality of product; Reduced the consumption of methyl alcohol and ammoniacal liquor, less environmental protection pressure.
The o-chlorobenzene glycine yield that utilizes method of the present invention preparation is up to (in o-chlorobenzaldehyde) more than 65%, and product is the crystalline powder of white or off-white color.
Embodiment
Below by embodiment, technical scheme of the present invention is described in further detail; But the present invention is not limited to these embodiment.
Embodiment 1
Getting methyl alcohol 42ml and bicarbonate of ammonia 23.5g drops in the there-necked flask, add 30% sodium cyanide solution 108g again, adding the back stirred 10 minutes, adding 67ml ammoniacal liquor stirred 10 minutes by constant temperature blender with magnetic force (Ying Yu of Gongyi City gives magnificent instrument plant and makes), then add the 25g o-chlorobenzaldehyde, stirred 20 minutes, be warming up to 30 ℃ of reactions 5 hours, be warming up to 80 ℃ then, reacted 4 hours, reaction finishes the back and concentrates in 70 ℃ of normal pressures, steam and in reaction flask, add tap water 83ml behind the cut 60ml, and add 30% the NaOH aqueous solution and regulate PH 〉=12 backs and heat up and catch up with ammonia, temperature to rise to 90 ℃ gradually to catch up with ammonia, catch up with about 2 hours of ammonia time, the ammonia water absorbs.
Catch up with behind the ammonia above-mentioned reaction solution is packed in the autoclave, the NaOH aqueous solution with 30% is warming up to 140 ℃ after regulating PH 〉=12, is pressure 0.4MPa, constant temperature hydrolysis 4.5 hours, and constant temperature finishes catching up with ammonia more than 90 ℃ 2 hours, and the ammonia water absorbs.
Discharging was decoloured to there-necked flask when macromolecule alkali for hydrolysis liquid was cooled to 90 ℃, maintain the temperature at 70 ℃, adding gac 1g decolours, filter, in decolouring filtrate, add the technical hydrochloric acid neutralization, 55 ℃ of controlled temperature, recording PH with acidometer (Shanghai Precision Scientific Apparatus Co., Ltd's manufacturing) had crystal to separate out at 9.5 o'clock, growing the grain 10 minutes, continuing processing industry hydrochloric acid then is 5.5 to recording PH with acidometer (Shanghai Precision Scientific Apparatus Co., Ltd's manufacturing), be cooled to 20 ℃, by SHZ-DC (III) circulation ability of swimming vacuum pump (Ying Yu of Gongyi City gives magnificent instrument plant and makes) suction filtration, filter cake washes with water once, and methyl alcohol is washed once, is vacuum-drying 10 hours in the vacuum drying oven (the gloomy reliable Instr Ltd. that tests in Shanghai) of 0.05Mpa～0.09Mpa in 70 ℃ in vacuum tightness, obtain the 22g o-chlorobenzene glycine, content 〉=99%, yield 67% (in o-chlorobenzaldehyde), product are the crystalline powder of white or off-white color.
Embodiment 2
Getting methyl alcohol 42ml and bicarbonate of ammonia 23.5g drops in the there-necked flask, add 30% sodium cyanide solution 108g again, adding the back stirred 15 minutes, adding 67ml ammoniacal liquor stirred 15 minutes, then add the 25g o-chlorobenzaldehyde, stirred 30 minutes, be warming up to 40 ℃ of reactions 4 hours, be warming up to 60 ℃ then, reacted 6 hours, reaction finishes the back and concentrates in 90 ℃ of normal pressures, in reaction flask, add tap water 83ml after steaming cut 90ml, and intensification catches up with ammonia, temperature to rise to 100 ℃ gradually after adding 30%KOH aqueous solution adjusting PH 〉=12, catch up with about 1.5 hours of ammonia time, the ammonia water absorbs.
Above-mentioned reaction solution is packed in the autoclave, be warming up to 130 ℃ after regulating PH 〉=12 with the 30%KOH aqueous solution, be pressure 0.3MPa, constant temperature hydrolysis 4 hours, constant temperature finishes to catch up with ammonia 1.5 hours at 100 ℃, and the ammonia water absorbs.
Discharging was decoloured to there-necked flask when macromolecule alkali for hydrolysis liquid was cooled to 85 ℃, maintain the temperature at 80 ℃, adding gac 1g decolours, filter, in decolouring filtrate, add the nitric acid neutralization, 70 ℃ of controlled temperature, recording PH with acidometer (Shanghai Precision Scientific Apparatus Co., Ltd's manufacturing) had crystal to separate out at 9.0 o'clock, growing the grain 30 minutes, continuing to add nitric acid then is 6.0 to recording PH with acidometer (Shanghai Precision Scientific Apparatus Co., Ltd's manufacturing), be cooled to 35 ℃, by SHZ-DC (III) circulation ability of swimming vacuum pump (Ying Yu of Gongyi City gives magnificent instrument plant and makes) suction filtration, filter cake washes with water once, and methyl alcohol is washed once, is vacuum-drying 8 hours in the vacuum drying oven (the gloomy reliable Instr Ltd. that tests in Shanghai) of 0.05Mpa～0.09Mpa in 80 ℃ in vacuum tightness, obtain the 23.8g o-chlorobenzene glycine, content 〉=99%, yield 72.5% (in o-chlorobenzaldehyde), product are the crystalline powder of white or off-white color.
Embodiment 3
Getting methyl alcohol 42ml and bicarbonate of ammonia 23.5g drops in the there-necked flask, add 30% sodium cyanide solution 108g again, adding the back stirred 12 minutes, adding 67ml ammoniacal liquor stirred 12 minutes, then add the 25g o-chlorobenzaldehyde, stirred 25 minutes, be warming up to 60 ℃ of reactions 5 hours, be warming up to 80 ℃ then, reacted 4 hours, reaction finishes the back and concentrates in 80 ℃ of normal pressures, steam and in reaction flask, add tap water 83ml behind the cut 70ml, and add 30% the NaOH aqueous solution and regulate PH 〉=12 backs and heat up and catch up with ammonia, temperature to rise to 120 ℃ gradually to catch up with ammonia, catch up with about 0.5 hour of ammonia time, the ammonia water absorbs.
Above-mentioned reaction solution is packed in the autoclave, and the NaOH aqueous solution with 30% is warming up to 170 ℃ after regulating PH 〉=12, its pressure 0.6MPa, and constant temperature hydrolysis 3 hours, constant temperature finishes catching up with ammonia more than 120 ℃ 0.5 hour, and the ammonia water absorbs.
Discharging was decoloured to there-necked flask when macromolecule alkali for hydrolysis liquid was cooled to 100 ℃, maintain the temperature at 90 ℃, adding gac 1g decolours, filter, in decolouring filtrate, add the sulfuric acid neutralization, 65 ℃ of controlled temperature, recording PH with acidometer (Shanghai Precision Scientific Apparatus Co., Ltd's manufacturing) had crystal to separate out at 8.8 o'clock, growing the grain 15 minutes, continuing to add sulfuric acid then is 5.8 to recording PH with acidometer (Shanghai Precision Scientific Apparatus Co., Ltd's manufacturing), be cooled to 30 ℃, by SHZ-DC (III) circulation ability of swimming vacuum pump (Ying Yu of Gongyi City gives magnificent instrument plant and makes) suction filtration, filter cake washes with water once, and methyl alcohol is washed once, is vacuum-drying 6 hours in the vacuum drying oven (the gloomy reliable Instr Ltd. that tests in Shanghai) of 0.05Mpa～0.09Mpa in 90 ℃ in vacuum tightness, obtain the 22.5g o-chlorobenzene glycine, content 〉=99%, yield 68.5% (in o-chlorobenzaldehyde), product are the crystalline powder of white or off-white color.
Specific embodiment described herein only is that the present invention's spirit is illustrated.The technician of the technical field of the invention can do various modifications or replenishes or adopt similar mode to substitute described specific embodiment, but can't depart from spirit of the present invention or surmount the defined scope of appended claims.
Although this paper has used cyaniding morely, basic hydrolysis, decolouring, the possibility of using other term do not got rid of in terms such as vacuum drying.Using these terms only is in order to describe and explain essence of the present invention more easily; They are construed to any additional restriction all is contrary with spirit of the present invention.
Claims (9)
1, a kind of preparation method of o-chlorobenzene glycine, this method may further comprise the steps:
A, cyaniding: get methyl alcohol and supercarbonate and join in the reactor, add cyanide salt solution and ammoniacal liquor then and then add under the condition that is warming up to 50 ℃～100 ℃ o-chlorobenzaldehyde earlier reacts 4～6 hours under temperature is 30 ℃～50 ℃ condition after and reacted 4～7 hours, the reaction back concentrates and obtains the cyaniding concentrated solution;
B, basic hydrolysis, decolouring: the cyaniding concentrated solution after above-mentioned concentrate was stirred 0.5～2 hour being warming up under the highly basic condition of pH value 〉=12 under 90 ℃～120 ℃ the condition; Be warming up to 120 ℃～170 ℃ then, control pressure is alkaline hydrolysis 3～8 hours under the condition of 0.2Mpa～0.6Mpa, and the hydrolysis rear decoloring obtains hydrolysate;
C, neutralization, crystallization: the hydrolysate of said hydrolyzed decolouring is neutralized to pH value 8～10 o'clock crystallization by acid under 50 ℃～70 ℃ condition, growing the grain 10～30 minutes continues to be neutralized to pH value 5.0～6.5 by acid and obtains the o-chlorobenzene glycine crystal;
D, suction filtration, oven dry: is 25 ℃～35 ℃ suction filtrations with the above-mentioned o-chlorobenzene glycine crystal that obtains in temperature, and solid obtains o-chlorobenzene glycine after by vacuum drying behind the suction filtration.
2, the preparation method of a kind of o-chlorobenzene glycine according to claim 1 is characterized in that: the supercarbonate described in the steps A is a kind of in bicarbonate of ammonia, sodium bicarbonate, the saleratus; Described cyanide salt solution is sodium cyanide solution, and its concentration is 20%～50%, and wherein the mol ratio of each reaction mass is an o-chlorobenzaldehyde: methyl alcohol: supercarbonate: cyanide salt: ammoniacal liquor is 1: 3～7: 1～3: 1～5: 1～5.
3, the preparation method of a kind of o-chlorobenzene glycine according to claim 1 and 2, it is characterized in that: stirred 8～15 minutes after in cyanide salt solution, adding ammoniacal liquor in the steps A, add o-chlorobenzaldehyde again and carry out cyanogenation under stirring condition, wherein adding the time of stirring behind the o-chlorobenzaldehyde is 15～30 minutes.
4, the preparation method of a kind of o-chlorobenzene glycine according to claim 1 is characterized in that: the thickening temperature described in the steps A is 50 ℃～100 ℃, and concentrated pressure is normal pressure.
5, the preparation method of a kind of o-chlorobenzene glycine according to claim 1 is characterized in that: the temperature of step B neutral and alkali hydrolysis is 130 ℃～150 ℃, and the basic hydrolysis time is 4～6 hours.
6, a kind of preparation method of o-chlorobenzene glycine according to claim 1 or 5, it is characterized in that: it is to stir 0.5～2 hour under 90 ℃～120 ℃ the condition in temperature that the hydrolysis of step B neutral and alkali finishes the back, be cooled to then under 70 ℃～90 ℃ the condition with behind the activated carbon decolorizing hydrolysate.
7, the preparation method of a kind of o-chlorobenzene glycine according to claim 1 is characterized in that: among the step C and used acid be a kind of in hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, the Hydrogen bromide.
8, the preparation method of a kind of o-chlorobenzene glycine according to claim 1 is characterized in that: the solid among the step D behind the suction filtration carries out vacuum drying by washing, methyl alcohol after washing.
9, according to the preparation method of claim 1 or 8 described a kind of o-chlorobenzene glycines, it is characterized in that: the temperature of the described vacuum drying of step D is 70 ℃～90 ℃, and drying time is 6～10 hours; Described vacuum tightness is 0.05Mpa～0.09Mpa.
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| CN107523594B (en) * | 2017-03-29 | 2018-08-28 | 武汉茵茂特生物技术有限公司 | The synthetic method of clopidogrel and its sulfate |
| CN111269134B (en) * | 2020-04-01 | 2022-09-20 | 九江中星医药化工有限公司 | Preparation method of phenylglycine and derivatives thereof |
| CN112174841B (en) * | 2020-11-09 | 2023-02-17 | 唐山晋广化工有限公司 | Production method of p-chlorophenylglycine |
| CN114685300A (en) * | 2020-12-31 | 2022-07-01 | 抚顺顺能化工有限公司 | Preparation method of o-chlorophenylglycine |
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Non-Patent Citations (2)
| Title |
|---|
| dl-邻氯苯基甘氨酸的合成研究. 马玉卓等.广东药学院学报，第22卷第3期. 2006 |
| dl-邻氯苯基甘氨酸的合成研究. 马玉卓等.广东药学院学报，第22卷第3期. 2006 * |
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Assignee: Changyi Hanying Medical Science Co.,Ltd. Assignor: Puluo Medicines Tech Co., Ltd., Zhejiang Contract record no.: 2011370000175 Denomination of invention: Method of preparing o-chlorophenyl glycine Granted publication date: 20091014 License type: Exclusive License Open date: 20071024 Record date: 20110510 |
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Effective date of registration: 20170713 Address after: 322118 Hengdian Industrial Zone, Jinhua, Zhejiang, China, Dongyang Patentee after: Zhejiang Apeloa Home Pharmaceutical Co.,Ltd. Address before: 322118 Zhejiang city of Dongyang province Hengdian Industrial Zone Zhejiang Apeloa Medical Technology Co Ltd Patentee before: Puluo Medicines Tech Co., Ltd., Zhejiang |
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Effective date of registration: 20200623 Address after: 322118 Hengdian Industrial Zone, Jinhua, Zhejiang, China, Dongyang Co-patentee after: APELOA PHARMACEUTICAL Co.,Ltd. Patentee after: ZHEJIANG APELOA JIAYUAN PHARMACEUTICAL Co.,Ltd. Address before: 322118 Hengdian Industrial Zone, Jinhua, Zhejiang, China, Dongyang Patentee before: ZHEJIANG APELOA JIAYUAN PHARMACEUTICAL Co.,Ltd. |