CN102050749B - Preparation and refining method of alpha-(N-benzyl-N-methyl amino)-m-hydroxyacetophenone hydrochloride - Google Patents
Preparation and refining method of alpha-(N-benzyl-N-methyl amino)-m-hydroxyacetophenone hydrochloride Download PDFInfo
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- CN102050749B CN102050749B CN 201010550931 CN201010550931A CN102050749B CN 102050749 B CN102050749 B CN 102050749B CN 201010550931 CN201010550931 CN 201010550931 CN 201010550931 A CN201010550931 A CN 201010550931A CN 102050749 B CN102050749 B CN 102050749B
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- benzyl
- hydroxy acetophenone
- methylamino
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- hydrochloride
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- QGHUDAOMXLLADV-UHFFFAOYSA-N 2-[benzyl(methyl)amino]-1-(3-hydroxyphenyl)ethanone;hydrochloride Chemical compound Cl.C=1C=CC=CC=1CN(C)CC(=O)C1=CC=CC(O)=C1 QGHUDAOMXLLADV-UHFFFAOYSA-N 0.000 title claims abstract description 29
- 238000000034 method Methods 0.000 title claims abstract description 20
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 238000007670 refining Methods 0.000 title abstract description 8
- 238000006243 chemical reaction Methods 0.000 claims abstract description 25
- 238000005893 bromination reaction Methods 0.000 claims abstract description 23
- 238000005576 amination reaction Methods 0.000 claims abstract description 16
- 239000002904 solvent Substances 0.000 claims abstract description 12
- LUJMEECXHPYQOF-UHFFFAOYSA-N 3-hydroxyacetophenone Chemical compound CC(=O)C1=CC=CC(O)=C1 LUJMEECXHPYQOF-UHFFFAOYSA-N 0.000 claims abstract description 11
- 230000003197 catalytic effect Effects 0.000 claims abstract description 11
- 238000009833 condensation Methods 0.000 claims abstract description 10
- 230000005494 condensation Effects 0.000 claims abstract description 10
- RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 claims abstract description 9
- 230000031709 bromination Effects 0.000 claims abstract description 8
- 239000002994 raw material Substances 0.000 claims abstract description 8
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 6
- 239000000126 substance Substances 0.000 claims abstract description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 20
- 239000012043 crude product Substances 0.000 claims description 17
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 13
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 12
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 12
- 238000009413 insulation Methods 0.000 claims description 12
- 239000000243 solution Substances 0.000 claims description 12
- 238000003756 stirring Methods 0.000 claims description 12
- 238000000967 suction filtration Methods 0.000 claims description 12
- 238000010792 warming Methods 0.000 claims description 12
- 238000006482 condensation reaction Methods 0.000 claims description 6
- 229910000042 hydrogen bromide Inorganic materials 0.000 claims description 6
- 238000000746 purification Methods 0.000 claims description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 6
- 235000017550 sodium carbonate Nutrition 0.000 claims description 6
- 238000010521 absorption reaction Methods 0.000 claims description 4
- 239000003513 alkali Substances 0.000 claims description 4
- 239000012267 brine Substances 0.000 claims description 4
- 239000012295 chemical reaction liquid Substances 0.000 claims description 4
- 238000004821 distillation Methods 0.000 claims description 4
- 239000000706 filtrate Substances 0.000 claims description 4
- 230000007935 neutral effect Effects 0.000 claims description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 claims description 4
- 230000003068 static effect Effects 0.000 claims description 4
- 239000002912 waste gas Substances 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 2
- 238000012546 transfer Methods 0.000 claims description 2
- 230000007613 environmental effect Effects 0.000 abstract description 3
- 239000002360 explosive Substances 0.000 abstract description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 abstract 2
- 239000003208 petroleum Substances 0.000 abstract 1
- 231100000331 toxic Toxicity 0.000 abstract 1
- 230000002588 toxic effect Effects 0.000 abstract 1
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- OCYSGIYOVXAGKQ-FVGYRXGTSA-N phenylephrine hydrochloride Chemical compound [H+].[Cl-].CNC[C@H](O)C1=CC=CC(O)=C1 OCYSGIYOVXAGKQ-FVGYRXGTSA-N 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 229960003733 phenylephrine hydrochloride Drugs 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000004904 shortening Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- ARKIFHPFTHVKDT-UHFFFAOYSA-N 1-(3-nitrophenyl)ethanone Chemical compound CC(=O)C1=CC=CC([N+]([O-])=O)=C1 ARKIFHPFTHVKDT-UHFFFAOYSA-N 0.000 description 1
- 108060003345 Adrenergic Receptor Proteins 0.000 description 1
- 102000017910 Adrenergic receptor Human genes 0.000 description 1
- DEOLOLRQXYCZFC-UHFFFAOYSA-N C1=CC=C(C=C1)COC2=CC=CC(=C2)C(=O)C=NO Chemical compound C1=CC=C(C=C1)COC2=CC=CC(=C2)C(=O)C=NO DEOLOLRQXYCZFC-UHFFFAOYSA-N 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- 208000006550 Mydriasis Diseases 0.000 description 1
- 208000003734 Supraventricular Tachycardia Diseases 0.000 description 1
- 238000001949 anaesthesia Methods 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000006193 diazotization reaction Methods 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- -1 inflammable Substances 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000036513 peripheral conductance Effects 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to preparation and a refining method of alpha-(N-benzyl-N-methyl amino)-m-hydroxyacetophenone hydrochloride. The alpha-(N-benzyl-N-methyl amino)-m-hydroxyacetophenone hydrochloride is prepared by performing catalytic bromination, amination condensation and a salifying reaction on m-hydroxyacetophenone, a bromizating agent and methyl benzyl amine which serve as main raw materials and single petroleum ether which serves as a solvent. The method has a simple and convenient process, uses readily available raw materials and avoids using chemical solvents such as inflammable solvents, explosive solvents, toxic solvents and the like in a preparation process. The alpha-(N-benzyl-N-methyl amino)-m-hydroxyacetophenone hydrochloride has the characteristics of high yield, high purity, low cost, environmental friendliness and the like.
Description
Technical field
The present invention relates to preparation and the process for purification of α-(N-benzyl-N-methylamino)-m-hydroxy acetophenone hydrochloride, belong to chemosynthesis technical field.
Background technology
Phenylephrine hydrochloride (Phenylephedrine Hydrochloride) has another name called neophryn, Phenylephrine Hydrochloride, is α type adrenergic receptor stimulant.It mainly increases peripheral vascular resistance, and local vascular is had contraction, makes elevation of blood pressure; In anaesthesia process, compare with Xylotox, to ask in the time of can shortening anesthesia induction, anaesthetic effect is good, and consumption is few, and side effect just reduces relatively; Also be used for supraventricular tachycardia and mydriasis inspection etc., this product all has larger market outlook in these treatments fields.
α-(N-benzyl-N-methylamino)-m-hydroxy acetophenone hydrochloride is the key intermediate of preparation phenylephrine hydrochloride, its synthetic method mainly contains at present: (1) is take 3-benzoxy benzoylformaldoxime as main raw material, make through reactions such as bromination, amination, hydrolysis, but in this reaction process, used the larger organic solvent of toxicity, as chloroform and benzene, and by product is difficult to remove clean, cause product purity not high (Sergievskaya, S.I.; Ravdel, G.A., Zhurnal Obshchei Khimii, 22,496-502.).(2) take the 3-hydroxy acetophenone as main raw material, make through reactions such as the benzoyl protection of bromination, hydroxyl, amination, hydrolysis deprotections, this method causes total recovery lower because reactions steps is long, and cost is higher, and the purity of product is not high.(Hukki，Jaakko；Honkanen，Erkki.Acta?Chemica?Scandinavica)。(3) take the 3-nitro-acetophenone as main raw material, make through reactions such as bromination, amination, shortening, diazotization, hydrolysis, this method reactions steps is long, side reaction is many, the three wastes are many, and also use inflammable, explosive solvent in reaction process, overall yield of reaction is low, the deficiencies (Sergievskaya, S.I.) such as cost is high and of poor quality.
Summary of the invention
The deficiency that exists for the method for prior art, as reactions steps is long, total recovery is low, cost is high, use the shortcomings such as toxicity larger organic solvent, post-processing difficulty are large, final product quality is poor, first purpose of the present invention is to provide the preparation method of a kind of simple process, cost is low, yield is high, the three wastes are few, environmental pollution is little α-(N-benzyl-N-methylamino)-m-hydroxy acetophenone hydrochloride.
In order to realize purpose of the present invention, the contriver gropes by lot of experiments, finally obtained the synthetic route of following a kind of α-(N-benzyl-N-methylamino)-m-hydroxy acetophenone hydrochloride: take m-hydroxy acetophenone, bromizating agent and methyl-benzyl amine as main raw material, take single sherwood oil as solvent, prepare α-(N-benzyl-N-methylamino)-m-hydroxy acetophenone hydrochloride crude product through catalytic bromination, amination condensation, salt-forming reaction.
Particularly, the chemical equation of said synthesis route is as follows:
(1) catalytic bromination reaction:
(2) amination condensation:
(3) salt-forming reaction:
Preferably, the preparation method of above-mentioned α-(N-benzyl-N-methylamino)-m-hydroxy acetophenone hydrochloride, wherein said catalytic bromination reactions steps is: mix sherwood oil, m-hydroxy acetophenone and 4 bromide, stir after being warming up to room temperature, drip C
5H
5NHBrBr
2, dropwise rear insulation 0.5-3h, namely get the bromide reaction solution.For environmental contamination reduction, the hydrogen bromide waste gas that described catalytic bromination reaction produces can be processed with alkali liquor absorption.
Preferably, the preparation method of above-mentioned α-(N-benzyl-N-methylamino)-m-hydroxy acetophenone hydrochloride, wherein said amination condensation step is: under room temperature condition, add entry and soda ash in bromination reaction liquid, transfer pH to neutral after stirring, static layering is removed lower floor's brine layer, then drip the N-methylbenzylamine, temperature control is in 30 ℃, and dropping is warming up to 45-50 ℃ after finishing, insulation 0.5-3h, suction filtration, filtrate are condensation reaction solution.
Preferably, the preparation method of above-mentioned α-(N-benzyl-N-methylamino)-m-hydroxy acetophenone hydrochloride, wherein said salt-forming reaction step is: add hydrochloric acid, temperature to be controlled in 40 ℃ in condensation reaction solution, adjust pH is to 2-3, heat temperature raising, normal pressure reclaims sherwood oil, cools to room temperature, and insulated and stirred 0.2-2h, through suction filtration, centrifugal, oven dry, get α-(N-benzyl-N-methylamino)-m-hydroxy acetophenone hydrochloride crude product.
Second purpose of the present invention is to provide the process for purification of a kind of α-(N-benzyl-N-methylamino)-m-hydroxy acetophenone hydrochloride crude product.Specific as follows:
The ethanol that adds 2-4 doubly to measure in α-(N-benzyl-N-methylamino)-m-hydroxy acetophenone hydrochloride crude product, being warming up to backflow and crude product all dissolves, ethanol 25-35% is reclaimed in air distillation, cool again to room temperature, stir insulation 0.2-2h, through suction filtration, centrifugal, oven dry, get α-(N-benzyl-N-methylamino)-m-hydroxy acetophenone hydrochloride elaboration.
Compared with prior art, the preparation of α of the present invention-(N-benzyl-N-methylamino)-m-hydroxy acetophenone hydrochloride and process for purification have following useful technique effect and progressive significantly:
(1) in preparation process, bromination reaction adds the catalyzer 4 bromide, does directly bromination of solvent with sherwood oil, has saved phenolic hydroxyl group protection and the deprotection reaction of old technology, has greatly reduced processing step, and total recovery is high, reduced cost.
(2) in the bromination reaction process, adopt novel bromizating agent C
5H
5NHBrBr
2With the catalyzer 4 bromide, improved the yield of bromination reaction, and bromination liquid is directly used in the next step, simplified operation process.
(3) the hydrolysis deprotection reaction of old technology has been saved in salt-forming reaction, has reduced processing step.
(4) in preparation process, solvent for use is single sherwood oil, has avoided the employing multi-solvents, is conducive to reclaim solvent, reduce costs, and also environmentally friendly.
Generally speaking, the preparation of α of the present invention-(N-benzyl-N-methylamino)-m-hydroxy acetophenone hydrochloride is compared with the method for prior art with process for purification, having simple process, raw material has removed from being easy to get, preparing and has used the organic solvents such as inflammable, explosive, poisonous, yield exceeds 10 percentage points than prior art, have the characteristics such as yield is high, purity good (content 〉=99%, HPLC detects), cost is low, environmental friendliness.
Embodiment
Be below specific embodiments of the invention, technical scheme of the present invention is done further the description, but protection scope of the present invention is not limited to these embodiment.Every do not deviate from the change of the present invention design or be equal to substitute include within protection scope of the present invention.
Synthesizing with refining of embodiment 1 α-(N-benzyl-N-methylamino)-m-hydroxy acetophenone hydrochloride
Sherwood oil: 400kg
M-hydroxy acetophenone: 68kg
4 bromide: 0.7kg
C
5H
5N·HBr·Br
2：80kg
Sodium carbonate: 30kg
N-methylbenzylamine: 121kg
Hydrochloric acid: 100kg
Ethanol: 300kg
(1) catalytic bromination reaction:
In the 1500L reactor, drop into 400kg sherwood oil and 68kg m-hydroxy acetophenone, add catalyzer 4 bromide 0.7kg, stir 0.5h after being warming up to room temperature, add bromizating agent C
5H
5NHBrBr
280kg, about 1h, the hydrogen bromide waste gas alkali liquor absorption of generation dropwises rear insulation 2h, namely gets the bromide reaction solution.
(2) amination condensation:
Above-mentioned bromination reaction liquid is transferred in the amination still, at ambient temperature, adds entry 50kg and soda ash 30kg, after stirring, adjust pH is to neutral, and after static 0.5h, layering divides and falls down a layer brine layer, then with the clear water washing once, divides to fall washing water; After layering was complete, beginning dripped N-methylbenzylamine 121kg in the amination still, and temperature control after dripping end, is warming up to 45-50 ℃ in 30 ℃, insulation 1h, and suction filtration, filtrate namely gets the reaction solution of condensation.
(3) salt-forming reaction:
Above-mentioned condensation reaction solution is transferred in salt oven, add hydrochloric acid 100kg, temperature in the kettle is controlled in 40 ℃, control the pH value to 2-3, heat temperature raising, normal pressure reclaims sherwood oil, cool to room temperature, insulated and stirred 0.5h through suction filtration, centrifugal, oven dry, gets α-(N-benzyl-N-methylamino)-m-hydroxy acetophenone hydrochloride crude product 100kg.
(4) crude product refining
α-(N-benzyl-N-methylamino)-m-hydroxy acetophenone hydrochloride crude product 100kg is transferred in refining kettle, add 300kg ethanol, being warming up to backflow and crude product all dissolves, ethanol approximately 30% is reclaimed in air distillation, cool again to room temperature, stir insulation 0.5h, through suction filtration, centrifugal, oven dry, get α-(N-benzyl-N-methylamino)-m-hydroxy acetophenone hydrochloride elaboration 95kg, content is 99.2%.
Synthesizing with refining of embodiment 2 α-(N-benzyl-N-methylamino)-m-hydroxy acetophenone hydrochloride
Sherwood oil: 400kg
M-hydroxy acetophenone: 70kg
4 bromide: 1.1kg
C
5H
5N·HBr·Br
2：90kg
Sodium carbonate: 30kg
N-methylbenzylamine: 130kg
Hydrochloric acid: 120kg
Ethanol: 310kg
(1) catalytic bromination reaction:
In the 1500L reactor, drop into 400kg sherwood oil and 70kg m-hydroxy acetophenone, add catalyzer 4 bromide 1.1kg, stir 0.5h after being warming up to room temperature, add bromizating agent C
5H
5NHBrBr
290kg, about 1h, the hydrogen bromide waste gas alkali liquor absorption of generation dropwises rear insulation 3h, namely gets the bromide reaction solution.
(2) amination condensation:
Above-mentioned bromination reaction liquid is transferred in the amination still, at ambient temperature, adds entry 50kg and soda ash 30kg, after stirring, adjust pH is to neutral, and after static 0.5h, layering divides and falls down a layer brine layer, then with the clear water washing once, divides to fall washing water; After layering was complete, beginning dripped N-methylbenzylamine 130kg in the amination still, and temperature control after dripping end, is warming up to 45-50 ℃ in 30 ℃, insulation 3h, and suction filtration, filtrate namely gets the reaction solution of condensation.
(3) salt-forming reaction:
Above-mentioned condensation reaction solution is transferred in salt oven, add hydrochloric acid 120kg, temperature in the kettle is controlled in 40 ℃, control the pH value to 2-3, heat temperature raising, normal pressure reclaims sherwood oil, cool to room temperature, insulated and stirred 2h through suction filtration, centrifugal, oven dry, gets α-(N-benzyl-N-methylamino)-m-hydroxy acetophenone hydrochloride crude product 105kg.
(4) crude product refining
α-(N-benzyl-N-methylamino)-m-hydroxy acetophenone hydrochloride crude product 105kg is transferred in refining kettle, add 310kg ethanol, being warming up to backflow and crude product all dissolves, ethanol approximately 30% is reclaimed in air distillation, cool again to room temperature, stir insulation 2h, through suction filtration, centrifugal, oven dry, get α-(N-benzyl-N-methylamino)-m-hydroxy acetophenone hydrochloride elaboration 106kg, content is 99.3%.
Claims (1)
1. the preparation method of α-(N-benzyl-N-methylamino)-m-hydroxy acetophenone hydrochloride, is characterized in that: with m-hydroxy acetophenone, bromizating agent C
5H
5NHBrBr
2, catalyzer 4 bromide and methyl-benzyl amine is raw material, take sherwood oil as solvent, is prepared from through catalytic bromination, amination, salt-forming reaction, its chemical equation is as follows:
(1) catalytic bromination reaction:
(2) amination condensation:
(3) salt-forming reaction:
Described catalytic bromination reactions steps is: mix sherwood oil, m-hydroxy acetophenone and 4 bromide, stir after being warming up to room temperature, drip C
5H
5NHBrBr
2, dropwise rear insulation 0.5-3 h, namely get the bromide reaction solution;
Described amination condensation step is: under room temperature condition, add entry and soda ash in bromination reaction liquid, transfer pH to neutral after stirring, static layering is removed lower floor's brine layer, then drip the N-methylbenzylamine, temperature control is in 30 ℃, and dropping is warming up to 45-50 ℃ after finishing, insulation 0.5-3 h, suction filtration, filtrate are condensation reaction solution;
Described salt-forming reaction step is: add hydrochloric acid in condensation reaction solution, temperature is controlled in 40 ℃, adjust pH is to 2-3, heat temperature raising, normal pressure reclaims sherwood oil, cools to room temperature, and insulated and stirred 0.2-2h, through suction filtration, centrifugal, oven dry, get α-(N-benzyl-N-methylamino)-m-hydroxy acetophenone hydrochloride crude product.
2. the preparation method of α as claimed in claim 1-(N-benzyl-N-methylamino)-m-hydroxy acetophenone hydrochloride, is characterized in that: the hydrogen bromide waste gas alkali liquor absorption that described catalytic bromination reaction produces.
3. the process for purification of α-(N-benzyl-N-methylamino)-m-hydroxy acetophenone hydrochloride crude product, it is characterized in that: the ethanol that adds 2-4 doubly to measure in described crude product, being warming up to backflow and crude product all dissolves, ethanol 25-35% is reclaimed in air distillation, cool again to room temperature, stir insulation 0.2-2h, through suction filtration, centrifugal, oven dry, get α-(N-benzyl-N-methylamino)-m-hydroxy acetophenone hydrochloride elaboration.
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| CN104356013A (en) * | 2014-11-18 | 2015-02-18 | 浙江海翔药业股份有限公司 | Preparation method of alpha-(N-methyl-N-benzylamino)-3-hydroxyacetophenone hydrochloride |
| CN117486739A (en) * | 2022-07-26 | 2024-02-02 | 武汉武药制药有限公司 | A kind of preparation method of impurities in phenylephrine hydrochloride raw material medicine |
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