CN102675132A - Preparation method of phenoxybenzamine hydrochloride - Google Patents
Preparation method of phenoxybenzamine hydrochloride Download PDFInfo
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- CN102675132A CN102675132A CN2012101705621A CN201210170562A CN102675132A CN 102675132 A CN102675132 A CN 102675132A CN 2012101705621 A CN2012101705621 A CN 2012101705621A CN 201210170562 A CN201210170562 A CN 201210170562A CN 102675132 A CN102675132 A CN 102675132A
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Abstract
The invention relates to a preparation method of phenoxybenzamine hydrochloride, which comprises the following steps of: 1) conducting etherification reaction to phenol and propylene epoxide at 60-85 DEG C and pH (potential of hydrogen) of 7-8 to produce phenoxy isopropanol; 2) conducting chlorination reaction to the phenoxy isopropanol and thionyl chloride to produce phenoxy isochloropropane; 3) conducting amination reaction to the phenoxy isochloropropane and 2-aminoethanol at 165-170 DEG C in polyethylene glycol solvent to produce N-(hydroxyl) ethylphenoxy isopropylamine; 4) conducting condensation reaction to the N-(hydroxyl) ethylphenoxy isopropylamine and benzyl chloride to produce N-hydroxyethyl-N-benzyl phenoxy isopropylamine; and 5) conducting salt forming reaction and chlorination reaction to the N-hydroxyethyl-N-benzyl phenoxy isopropylamine to produce N-chloroethyl-N-benzyl phenoxy isopropylamine hydrochloride, i.e. the phenoxybenzamine hydrochloride. The preparation method of phenoxybenzamine hydrochloride has the advantages of simple process line, low cost and high yield, and is suitable for the industrial production of the phenoxybenzamine hydrochloride.
Description
Technical field
The present invention relates to a kind of preparation method of phenoxybenzamine hydrochloride.
Background technology
Phenoxybenzamine hydrochloride, chemical name are N-(1-methyl-2-benzene oxygen ethyl)-N-(2-chloroethyl) benzene methanamine hydrochloride, and molecular formula is C
18H
22ClNOHCl, structural formula is following:
Phenoxybenzamine hydrochloride is the alpha receptor blocking medicine, and the clinical periperal vascular spasm that is used for also can be used for shock and pheochromocytoma.Also do not see at present Chinese patent report about the preparation method of phenoxybenzamine hydrochloride.
Summary of the invention
Technical problem to be solved by this invention overcomes the deficiency of prior art, provides that a kind of operational path is simple, cost is low, yield is high, is suitable for the preparation method of the phenoxybenzamine hydrochloride of suitability for industrialized production.
For solving above technical problem, the following technical scheme that the present invention takes:
A kind of preparation method of phenoxybenzamine hydrochloride, it comprises the steps:
(1), makes phenol and propylene oxide time carry out etherification reaction and generate the phenoxy Virahol in 60～85 ℃ of temperature, pH7 ~ 8;
(2), make step (1) gained phenoxy Virahol and thionyl chloride generation chlorination reaction generate the different chloropropane of phenoxy;
(3), make different chloropropane of step (2) gained phenoxy and 2-monoethanolamine in the polyoxyethylene glycol solvent, carry out amination reaction under 165～170 ℃ of the temperature and generate N-hydroxyethyl phenoxy Isopropylamine;
(4), make the reaction of step (3) gained N-hydroxyethyl phenoxy Isopropylamine and Benzyl Chloride that condensation reaction take place and generate N-hydroxyethyl-N-benzyl phenoxy Isopropylamine;
(5), make step (4) gained N-hydroxyethyl-N-benzyl phenoxy Isopropylamine generation salt-forming reaction and chlorination generate N-chloroethyl-N-benzyl phenoxy isopropylamine hydrochloride, i.e. phenoxybenzamine hydrochloride,
The preparation method of said phenoxybenzamine hydrochloride representes as follows with chemical equation:
According to further embodiment of the present invention:
In the step (1), the molar ratio of phenol and propylene oxide is 1:1.4 ~ 1.5.The practical implementation process of step (1) is following: in etherifying reactor, add phenol, Pottasium Hydroxide or sodium hydroxide, water, heating is all dissolved phenol, drips propylene oxide, is heated to 60～65 ℃ of reactions 3 ~ 4 hours; Reheat to 80～85 ℃ reaction 1 ~ 2 hour, cooling, still is extracted in the blowing suction, adds water; Use methylbenzene extraction, washing is reclaimed toluene to most; The cut of 125～130 ℃/21mmHg is collected in molecular distillation, gets transparent viscous fluid, is the phenoxy Virahol.
The practical implementation process of step (2) is following: in the chlorination reaction still, add the phenoxy Virahol, stir, refrigated cooling is in dripping thionyl chloride below 20 ℃, room temperature reaction 2 ~ 4 hours; Hold over night adds the acid binding agent pyridine, stirs, and temperature rising reflux 2 ~ 4 hours is when temperature rises to 90 ℃; Be cooled to below 30 ℃, pot is extracted in the blowing suction, adds water, uses methylbenzene extraction; Washing is transferred pH to 7～8 with saturated saleratus solution again, and static layering is used water washing; Reclaim toluene to most, molecular distillation, the cut of 96～112 ℃/9mmHg of collection gets little yellow transparent liquid and is the different chloropropane of phenoxy.
The practical implementation process of step (3) is following: in reaction kettle, add the 2-monoethanolamine, and polyoxyethylene glycol, oil bath is heated to 145～150 ℃, stirs to drip the different chloropropane of phenoxy down; Finish, be warming up to 165～170 ℃ of reactions 4 ~ 6 hours, be cooled to put into water below 120 ℃; Use methylbenzene extraction, organic layer is used water washing, and to extracting solution pH 2～3, acid extraction liquid is neutralized to pH 10～11 with 20wt% ~ 35wt% sodium hydroxide solution to methylbenzene extraction liquid with 5wt% ~ 10wt% hydrochloric acid extraction; Use methylbenzene extraction again, washing is sloughed moisture with Calcium Chloride Powder Anhydrous, filters; After filtrating boils off toluene, add ETHYLE ACETATE and sherwood oil, the two adds weight ratio is ETHYLE ACETATE: sherwood oil=1.5 ~ 2.5:1, crystallization; Get rid of filter below 20 ℃, get white crystalline powder, be N-hydroxyethyl phenoxy Isopropylamine.
The practical implementation process of step (4) is following: in reaction kettle, add N-hydroxyethyl phenoxy Isopropylamine, Benzyl Chloride, polyoxyethylene glycol, salt of wormwood and absolute ethyl alcohol stir temperature rising reflux; Reaction finishes, and boils off ethanol, and cooling adds water; Use methylbenzene extraction, behind the washing toluene layer, add 5wt% ~ 15wt% hydrochloric acid and transfer pH to 2～3, leave standstill; Tell the sour water layer, methylbenzene extraction is used in sour water layer liquid feeding adjusting PH with base to 11～12, washing; Boil off toluene, get light yellow dope, be N-hydroxyethyl-N-benzyl phenoxy Isopropylamine.
The number-average molecular weight of above-mentioned polyoxyethylene glycol can be 400
The practical implementation process of step (5) is following: in reaction kettle, add N-hydroxyethyl-N-benzyl phenoxy Isopropylamine, solvent chloroform, stir cooling and feed dry hydrogen chloride gas to pH 4～5 down, in dripping thionyl chloride below 20 ℃, dropwise; Slowly heat up, be incubated 2 ~ 4 hours down, be cooled to below 30 ℃, in the suction still pot at 55 ~ 65 ℃; It is closely most to reclaim chloroform, adds the mixed solvent of ethanol and ether, crystallisation by cooling; Get rid of filter below 20 ℃, drying gets the phenoxybenzamine hydrochloride bullion.
Further, described preparation method also comprises the phenoxybenzamine hydrochloride bullion is carried out the purified step.One of purified is concrete following with preferred process: adding phenoxybenzamine hydrochloride bullion in reaction kettle, and ethanol, weight is 0.3 ~ 0.4 times ether, gac of ethanol weight, opens stirring; Be warmed up to 55～58 ℃ of insulation 0.5 ~ 2h, press filtration is while hot pressed and is finished, and reaction kettle is cooled to below 25 ℃; Add ether again, cold pressing and filter to crystallizing pan, stir crystallisation by cooling; Get rid of material below 20 ℃, drying gets the phenoxybenzamine hydrochloride finished product.
Owing to take above technical scheme, the present invention compared with prior art has following advantage:
The preparation method of phenoxybenzamine hydrochloride provided by the invention, operational path is simple, cost is low, yield is high, is suitable for the suitability for industrialized production phenoxybenzamine hydrochloride.
Embodiment
Below in conjunction with concrete embodiment the present invention is done further detailed explanation, but the invention is not restricted to following examples.
Embodiment 1 etherification reaction
(1) feeding intake of etherification reaction referring to table 1:
Table 1
| The supplementary material title | Charging capacity Kg | Feed ratio | The supplementary material title | Charging capacity Kg | Feed ratio |
| Phenol | 50 | 1 | Water | 1.5 | 0.03 |
| Propylene oxide | 37 | 0.74 | Toluene | 100×2 | 4 |
| Pottasium Hydroxide | 1.5 | 0.03 | Water | 50×3 | 3 |
(2) practical implementation process is following:
In the 100L etherifying reactor, add phenol 50Kg, Pottasium Hydroxide 1.5Kg, water 1.5Kg; Be heated to 50 ± 1 ℃ phenol is all dissolved, drip propylene oxide 37Kg, control about 1 hour and drip off; Be heated to 60～65 ℃ of reactions 3 hours, reheat to 80～85 ℃ reaction 2 hours.Cooling, blowing suction 500L extracts still, adds water 50Kg, with methylbenzene extraction 2 times; 100Kg/ time, washing twice, each 50Kg; Reclaim toluene to most, the cut of 125～130 ℃/21mm is collected in molecular distillation, gets transparent viscous fluid; Be phenoxy Virahol 68～72Kg, content >=95%, refractive index 1.5243～1.5254.
Embodiment 2 chlorination reactions
(1) feeding intake of chlorination reaction referring to table 2:
Table 2
| The supplementary material title | Charging capacity Kg | Feed ratio | The supplementary material title | Charging capacity Kg | Feed ratio |
| The phenoxy Virahol | 68～72 | 1 | Toluene | 210 | 3 |
| Thionyl chloride | 67 | 0.94 | Saturated sodium bicarbonate | In right amount | |
| Pyridine | 0.7 | 0.01 | Water | 100×4 | 5.7 |
(2) practical implementation process is following:
In 300L chlorination reaction still, add phenoxy Virahol 68～72Kg, stir, refrigated cooling, in dripping thionyl chloride 67Kg below 20 ℃, control is dripped the about 2h of speed and is dropwised.Room temperature reaction 3 hours, hold over night.Add pyridine 0.7Kg, stir, temperature rising reflux 3 hours when temperature rises to 90 ℃, is cooled to 30 ℃; Blowing suction 500L extracts pot, adds water 100Kg and extracts with toluene 210Kg, and water 100Kg washing 1 time is transferred pH to 7～8 with saturated saleratus solution again; Static layering with water washing 2 times, 100Kg/ time, reclaims toluene to most; Molecular distillation, the cut of 96～112 ℃/9mm of collection gets little yellow transparent liquid and is the different chloropropane 65～69Kg of phenoxy, content >=95%.
Embodiment 3 amination reactions
(1) feeding intake of amination reaction referring to table 3:
Table 3
| The supplementary material title | Charging capacity Kg | Feed ratio | The supplementary material title | Charging capacity Kg | Feed ratio |
| The different chloropropane of phenoxy | 65～69 | 1 | 7.5% hydrochloric acid | In right amount | |
| The 2-monoethanolamine | 72.5 | 1.08 | 30% sodium hydroxide | In right amount | |
| Polyoxyethylene glycol | 3.4 | 0.05 | Calcium Chloride Powder Anhydrous | In right amount |
| Water | ?140×4 | 8.3 | ETHYLE ACETATE | 46 | 0.68 |
| Toluene | ?100×2×2 | 5.9 | Sherwood oil | 23 | 0.34 |
(2) practical implementation process is following:
In the 200L reaction kettle, add 2-monoethanolamine 72.5Kg, polyoxyethylene glycol 3.4Kg, oil bath is heated to 145～150 ℃, stirs to drip the different chloropropane 65～69kg of phenoxy down, and control is dripped the about 2h of speed and is dripped off.Be warming up to 165～170 ℃ of reactions 5 hours.Be cooled to 120 ℃, put into 140Kg water.With methylbenzene extraction 2 times, each 100Kg.Organic layer water 140Kg washing 1 time, to extracting solution pH 2～3, acid extraction liquid is neutralized to pH10～11 with 30% sodium hydroxide solution to methylbenzene extraction liquid with 7.5% hydrochloric acid extraction, uses methylbenzene extraction again 2 times, each 100Kg.Methylbenzene extraction liquid is with water washing 2 times for the second time, and each 140Kg sloughs moisture with Calcium Chloride Powder Anhydrous, filters in 2 hours.After filtrating boils off toluene, add ETHYLE ACETATE 46Kg, sherwood oil 23Kg, crystallization is got rid of filter for 20 ℃, gets white crystalline powder 46～49kg and is N-hydroxyethyl phenoxy Isopropylamine, 69～73 ℃ of fusing points, content >=98%.
Embodiment 4 condensation reactions
(1) feeding intake of condensation reaction referring to table 4:
| The supplementary material title | Charging capacity Kg | Feed ratio | The supplementary material title | Charging capacity Kg | Feed ratio |
| N-hydroxyethyl phenoxy Isopropylamine | 46～49 | 1 | Water | 400 | 8.42 |
| Benzyl Chloride | 32.8 | 0.69 | Water | 200×4 | 16.84 |
| Polyoxyethylene glycol | 3.6 | 0.075 | Toluene | 200×4 | 16.84 |
| Salt of wormwood | 19 | 0.4 | 10% hydrochloric acid | In right amount | |
| Absolute ethyl alcohol | 380 | 8 | 30% liquid caustic soda | In right amount |
(2) practical implementation process is following:
In the 500L reaction kettle, add N-hydroxyethyl phenoxy Isopropylamine 46～49Kg, Benzyl Chloride 32.8Kg, polyoxyethylene glycol 3.6Kg, salt of wormwood 19Kg and absolute ethyl alcohol 380Kg stir, and are warming up to 78 ℃ and reflux 10 hours.Boil off ethanol, cooling adds water 400Kg.With methylbenzene extraction 2 times, each 200Kg, combining methylbenzene layer be with water washing 2 times, at every turn 200Kg.Toluene layer adds 10% hydrochloric acid and transfers pH to 2～3, and static 30 minutes, tell the sour water layer, the sour water layer adds 30% liquid adjusting PH with base to 11～12, and with methylbenzene extraction 2 times, each 200Kg, toluene layer be with water washing 2 times, at every turn 200Kg.Boil off toluene, get light yellow dope 69～73.5Kg, be N-hydroxyethyl-N-benzyl phenoxy Isopropylamine, content >=97%.
Embodiment 5 salifies and chlorination
(1) salify and chlorination feeds intake referring to table 5
(2) practical implementation process is following:
In 300L chlorination pot reaction kettle, add N-hydroxyethyl-N-benzyl phenoxy Isopropylamine 69～73.5Kg, chloroform 356Kg, stir cooling and feed dry hydrogen chloride gas to pH4～5 down, under 20 ℃, drip thionyl chloride 34.2Kg, control is dripped the about 1.5h of speed and is dripped off.Dropwise, slowly heat up, 60 ± 2 ℃ are incubated 3 hours, are cooled in 30 ℃ of suction still pots, and it is closely most to reclaim chloroform, adds ethanol 71Kg, ether 57Kg, and crystallisation by cooling, 20 ℃ are got rid of filter, and drying gets phenoxybenzamine hydrochloride bullion 51～55Kg.This phenoxybenzamine hydrochloride bullion is the off-white color crystalline powder, and odorless is almost tasteless.133～138 ℃ of fusing points, weight loss on drying≤1.0%.
Embodiment 6 purification step
In the 500L reaction kettle, add phenoxybenzamine hydrochloride bullion 51～55Kg, ethanol 88Kg, ether 32Kg, gac 2.6Kg open to stir and are warmed up to 55～58 ℃ of insulation 1h; Press filtration is while hot pressed and is finished, and reaction kettle is cooled to 25 ℃; Add ether 40Kg again, cold pressing and filter to crystallizing pan, stir 30 minutes crystallisation by cooling; 20 ℃ are got rid of material, get phenoxybenzamine hydrochloride tide article 40.5～46Kg, are drying to obtain the phenoxybenzamine hydrochloride finished product.
More than the present invention has been done detailed description; Its purpose is to let the personage that is familiar with this art can understand content of the present invention and implements; Can not limit protection scope of the present invention with this; All equivalences of doing according to spirit of the present invention change or modify, and all should be encompassed in protection scope of the present invention.
Claims (10)
1. the preparation method of a phenoxybenzamine hydrochloride, it is characterized in that: said preparation method comprises the steps:
(1), makes phenol and propylene oxide time carry out etherification reaction and generate the phenoxy Virahol in 60～85 ℃ of temperature, pH7 ~ 8;
(2), make step (1) gained phenoxy Virahol and thionyl chloride generation chlorination reaction generate the different chloropropane of phenoxy;
(3), make different chloropropane of step (2) gained phenoxy and 2-monoethanolamine in the polyoxyethylene glycol solvent, carry out amination reaction under 165～170 ℃ of the temperature and generate N-hydroxyethyl phenoxy Isopropylamine;
(4), make the reaction of step (3) gained N-hydroxyethyl phenoxy Isopropylamine and Benzyl Chloride that condensation reaction take place and generate N-hydroxyethyl-N-benzyl phenoxy Isopropylamine;
(5), make step (4) gained N-hydroxyethyl-N-benzyl phenoxy Isopropylamine generation salt-forming reaction and chlorination generate N-chloroethyl-N-benzyl phenoxy isopropylamine hydrochloride, i.e. phenoxybenzamine hydrochloride,
The preparation method of said phenoxybenzamine hydrochloride representes as follows with chemical equation:
2. the preparation method of phenoxybenzamine hydrochloride according to claim 1, it is characterized in that: in the step (1), the molar ratio of phenol and propylene oxide is 1: 1.4-1.5.
3. the preparation method of phenoxybenzamine hydrochloride according to claim 1 and 2, it is characterized in that: the practical implementation process of step (1) is following: in etherifying reactor, add phenol, Pottasium Hydroxide or sodium hydroxide, water, heating is all dissolved phenol; Drip propylene oxide, be heated to 60～65 ℃ of reactions 3 ~ 4 hours, reheat to 80～85 ℃ reaction 1 ~ 2 hour; Cooling, still is extracted in the blowing suction, adds water; Use methylbenzene extraction, washing is reclaimed toluene to most; The cut of 125～130 ℃/21mmHg is collected in molecular distillation, gets transparent viscous fluid, is the phenoxy Virahol.
4. the preparation method of phenoxybenzamine hydrochloride according to claim 1, it is characterized in that: the practical implementation process of step (2) is following: in the chlorination reaction still, add the phenoxy Virahol, stir refrigated cooling; In dripping thionyl chloride below 20 ℃, room temperature reaction 2 ~ 4 hours, hold over night adds the acid binding agent pyridine; Stir, temperature rising reflux 2 ~ 4 hours when temperature rises to 90 ℃, is cooled to below 30 ℃; Pot is extracted in the blowing suction, adds water, uses methylbenzene extraction, washing; Transfer pH to 7～8 with saturated saleratus solution again, static layering is used water washing, reclaims toluene to most; Molecular distillation, the cut of 96～112 ℃/9mmHg of collection gets little yellow transparent liquid and is the different chloropropane of phenoxy.
5. the preparation method of phenoxybenzamine hydrochloride according to claim 1, it is characterized in that: the practical implementation process of step (3) is following: in reaction kettle, add the 2-monoethanolamine, polyoxyethylene glycol, oil bath is heated to 145～150 ℃; Stir down and drip the different chloropropane of phenoxy, finish, be warming up to 165～170 ℃ of reactions 4 ~ 6 hours, be cooled to below 120 ℃; Put into water, use methylbenzene extraction, organic layer is used water washing, methylbenzene extraction liquid with 5wt% ~ 10wt% hydrochloric acid extraction to extracting solution pH 2～3; Acid extraction liquid is neutralized to pH 10～11 with 20wt% ~ 35wt% sodium hydroxide solution, uses methylbenzene extraction again, washing; Slough moisture with Calcium Chloride Powder Anhydrous, filter, after filtrating boils off toluene; Add ETHYLE ACETATE and sherwood oil, the two adds weight ratio is ETHYLE ACETATE: sherwood oil=1.5 ~ 2.5:1, crystallization; Get rid of filter below 20 ℃, get white crystalline powder, be N-hydroxyethyl phenoxy Isopropylamine.
6. the preparation method of phenoxybenzamine hydrochloride according to claim 1, it is characterized in that: the practical implementation process of step (4) is following: in reaction kettle, add N-hydroxyethyl phenoxy Isopropylamine, Benzyl Chloride, polyoxyethylene glycol, salt of wormwood and absolute ethyl alcohol stir; Temperature rising reflux, reaction finishes, and boils off ethanol, cooling; Add water, use methylbenzene extraction, behind the washing toluene layer, add 5wt% ~ 15wt% hydrochloric acid and transfer pH to 2～3; Leave standstill, tell the sour water layer, methylbenzene extraction is used in sour water layer liquid feeding adjusting PH with base to 11～12; Washing boils off toluene, gets light yellow dope, is N-hydroxyethyl-N-benzyl phenoxy Isopropylamine.
7. according to the preparation method of claim 5 or 6 described phenoxybenzamine hydrochlorides, it is characterized in that: the number-average molecular weight of described polyoxyethylene glycol is 400.
8. the preparation method of phenoxybenzamine hydrochloride according to claim 1, it is characterized in that: the practical implementation process of step (5) is following: in reaction kettle, add N-hydroxyethyl-N-benzyl phenoxy Isopropylamine, solvent chloroform, stir cooling and feed dry hydrogen chloride gas down to pH 4～5; In dripping thionyl chloride below 20 ℃, dropwise, slowly heat up; Be incubated 2 ~ 4 hours down at 55 ~ 65 ℃, be cooled to below 30 ℃, in the suction still pot; It is closely most to reclaim chloroform, adds the mixed solvent of ethanol and ether, crystallisation by cooling; Get rid of filter below 20 ℃, drying gets the phenoxybenzamine hydrochloride bullion.
9. the preparation method of phenoxybenzamine hydrochloride according to claim 8 is characterized in that: described preparation method also comprises said phenoxybenzamine hydrochloride bullion is carried out the purified step.
10. the preparation method of phenoxybenzamine hydrochloride according to claim 9, it is characterized in that: described purified detailed process is following: in reaction kettle, add the phenoxybenzamine hydrochloride bullion, ethanol, weight is 0.3 ~ 0.4 times ether, gac of ethanol weight; Open stirring, be warmed up to 55～58 ℃ of insulations 0.5 ~ 2h, press filtrations while hot; Press and finish, reaction kettle is cooled to add ether again below 25 ℃; Cold pressing and filter to crystallizing pan, stir crystallisation by cooling; Get rid of material below 20 ℃, drying gets the phenoxybenzamine hydrochloride finished product.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018130942A1 (en) * | 2017-01-16 | 2018-07-19 | Aurobindo Pharma Limited | A process for the preparation of phenoxybenzamine |
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| US2599000A (en) * | 1950-09-02 | 1952-06-03 | Smith Kline French Lab | Nu, nu-disubstituted-beta-halo-alkylamines |
| CN1347864A (en) * | 2001-10-15 | 2002-05-08 | 中国科学院大连化学物理研究所 | Synthesis of phenylate alcohol compounds |
| CN1961870A (en) * | 2006-12-01 | 2007-05-16 | 北京联合大学生物化学工程学院 | Method for preparing sustained releasing microcapsule of phenoxybenzamine hydrochloride and ethyl cellulose |
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2012
- 2012-05-29 CN CN2012101705621A patent/CN102675132A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US2599000A (en) * | 1950-09-02 | 1952-06-03 | Smith Kline French Lab | Nu, nu-disubstituted-beta-halo-alkylamines |
| CN1347864A (en) * | 2001-10-15 | 2002-05-08 | 中国科学院大连化学物理研究所 | Synthesis of phenylate alcohol compounds |
| CN1961870A (en) * | 2006-12-01 | 2007-05-16 | 北京联合大学生物化学工程学院 | Method for preparing sustained releasing microcapsule of phenoxybenzamine hydrochloride and ethyl cellulose |
Non-Patent Citations (1)
| Title |
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| CRIST N. FILER等: "THE PREPARATION AND CHARACTERIZATION OF (±)-[ PHENOXY -3H(N)]PHENOXYB ENZAMINE HYDROCHLORIDE AT HIGH SPECIFIC ACTIVITY1", 《JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICAL》 * |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2018130942A1 (en) * | 2017-01-16 | 2018-07-19 | Aurobindo Pharma Limited | A process for the preparation of phenoxybenzamine |
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Application publication date: 20120919 |