CN115784907A - Preparation method of DL-phenylephrine - Google Patents
Preparation method of DL-phenylephrine Download PDFInfo
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- CN115784907A CN115784907A CN202211553599.2A CN202211553599A CN115784907A CN 115784907 A CN115784907 A CN 115784907A CN 202211553599 A CN202211553599 A CN 202211553599A CN 115784907 A CN115784907 A CN 115784907A
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- SONNWYBIRXJNDC-UHFFFAOYSA-N 3-[1-Hydroxy-2-(methylamino)ethyl]phenol Chemical compound CNCC(O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-UHFFFAOYSA-N 0.000 title claims abstract description 22
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 238000006243 chemical reaction Methods 0.000 claims abstract description 39
- IAVREABSGIHHMO-UHFFFAOYSA-N 3-hydroxybenzaldehyde Chemical compound OC1=CC=CC(C=O)=C1 IAVREABSGIHHMO-UHFFFAOYSA-N 0.000 claims abstract description 28
- 238000003756 stirring Methods 0.000 claims abstract description 26
- 238000000034 method Methods 0.000 claims abstract description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000002904 solvent Substances 0.000 claims abstract description 20
- 238000001816 cooling Methods 0.000 claims abstract description 19
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 claims abstract description 18
- 229940125782 compound 2 Drugs 0.000 claims abstract description 16
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims abstract description 16
- 238000001035 drying Methods 0.000 claims abstract description 15
- 230000008569 process Effects 0.000 claims abstract description 14
- 229940126214 compound 3 Drugs 0.000 claims abstract description 13
- 238000001914 filtration Methods 0.000 claims abstract description 11
- 239000007788 liquid Substances 0.000 claims abstract description 10
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 claims abstract description 9
- 229930040373 Paraformaldehyde Natural products 0.000 claims abstract description 9
- 108010077895 Sarcosine Proteins 0.000 claims abstract description 9
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 claims abstract description 9
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims abstract description 9
- 229920002866 paraformaldehyde Polymers 0.000 claims abstract description 9
- 229940043230 sarcosine Drugs 0.000 claims abstract description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims abstract description 7
- 239000002253 acid Substances 0.000 claims abstract description 7
- 239000011230 binding agent Substances 0.000 claims abstract description 7
- 238000010992 reflux Methods 0.000 claims abstract description 7
- 238000010438 heat treatment Methods 0.000 claims abstract description 6
- 229940125904 compound 1 Drugs 0.000 claims abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 4
- 229940079593 drug Drugs 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 238000000605 extraction Methods 0.000 abstract description 2
- 238000000926 separation method Methods 0.000 abstract description 2
- 238000005904 alkaline hydrolysis reaction Methods 0.000 abstract 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 abstract 1
- 238000007142 ring opening reaction Methods 0.000 abstract 1
- 239000012074 organic phase Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 239000012065 filter cake Substances 0.000 description 6
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 6
- 229960001802 phenylephrine Drugs 0.000 description 5
- 230000009471 action Effects 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 238000002386 leaching Methods 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 3
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 238000011914 asymmetric synthesis Methods 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000003912 environmental pollution Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- LUJMEECXHPYQOF-UHFFFAOYSA-N 3-hydroxyacetophenone Chemical compound CC(=O)C1=CC=CC(O)=C1 LUJMEECXHPYQOF-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 208000003734 Supraventricular Tachycardia Diseases 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- -1 lithium aluminum hydride Chemical compound 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 239000002637 mydriatic agent Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000006462 rearrangement reaction Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 206010047302 ventricular tachycardia Diseases 0.000 description 1
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Abstract
The invention relates to the technical field of medicines, and discloses a preparation method of DL-phenylephrine, which comprises the following steps: adding m-hydroxybenzaldehyde (compound 1) into a reaction bottle, adding a solvent and an acid-binding agent, stirring and cooling to 0-10 ℃, dropwise adding benzoyl chloride, controlling the temperature to 0-10 ℃, stirring and reacting, adding water to extract and separate liquid after the reaction is finished, adding n-hexane, cooling and crystallizing, filtering, and drying to obtain a compound 2; adding the compound 2 and a solvent into a reaction bottle, adding sarcosine and paraformaldehyde under stirring, heating to reflux for carrying out water diversion reaction for 3-6h, cooling after the reaction is finished, adding water for extraction and liquid separation, drying with anhydrous sodium sulfate, and concentrating under reduced pressure to obtain a compound 3; and (3) carrying out ring opening on the compound 3 by hydrazine hydrate and removing benzoyl protection by alkaline hydrolysis to obtain DL phenylephrine. The preparation method of DL-phenylephrine has the advantages of simple process, mild reaction conditions, wide application prospect, high purity of the obtained product and high yield.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to a preparation method of DL-phenylephrine.
Background
Phenylephrine, is used primarily to treat paroxysmal supraventricular tachycardia and as a fast-acting mydriatic agent during fundus examination.
The phenylephrine molecule contains a chiral center, so that two enantiomers, R-phenylephrine and S-phenylephrine, exist, and R-phenylephrine, which is mainly physiologically active, is present.
Currently, the synthesis of phenylephrine mainly comprises a resolution method and an asymmetric synthesis method.
The resolution method has three routes, one is that m-hydroxybenzaldehyde is used as raw material, and single enantiomer product is obtained by rearrangement reaction and then resolution; secondly, m-hydroxybenzaldehyde is used as a raw material, corresponding raceme is obtained by amide reduction reaction under the action of lithium aluminum hydride, and a single enantiomer product is obtained by resolution with tartaric acid. And thirdly, synthesizing racemic phenylephrine by taking m-hydroxyacetophenone as a raw material through steps of palladium-carbon hydrogenation reduction and the like, and obtaining a single enantiomer product through tartaric acid resolution. The resolution method is widely applied, but has the problems that the theoretical yield is lower than 50 percent, and the resolved S-enantiomer can not be utilized, thereby wasting raw materials. In addition, the resolution method has complicated steps, and mother liquor in each step is not easy to treat, so that the problems of low yield, high cost, serious environmental pollution, low optical purity of products and the like are caused.
The asymmetric synthesis method mainly utilizes a chiral metal catalyst to carry out hydrogenation reduction to obtain a single-configuration product, the commonly used chiral catalyst is expensive transition metal and chiral ligand, the cost is high, and meanwhile, the environmental pollution is serious, so that the preparation method of the DL-phenylephrine is provided.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides a preparation method of DL-phenylephrine, which comprises the following steps:
step one, adding m-hydroxybenzaldehyde (compound 1) into a reaction bottle, adding a solvent and an acid-binding agent, stirring and cooling to 0-10 ℃, dropwise adding benzoyl chloride, controlling the temperature to 0-10 ℃, stirring and reacting, adding water to extract and separate liquid after the reaction is finished, adding n-hexane, cooling and crystallizing, filtering, and drying to obtain a compound 2;
adding the compound 2 and a solvent into a reaction bottle, stirring, adding sarcosine and paraformaldehyde, heating to reflux, carrying out water diversion reaction for 3-6h, cooling after the reaction is finished, adding water, extracting, separating liquid, drying with anhydrous sodium sulfate, and concentrating under reduced pressure to obtain a compound 3;
and step three, adding the compound 3 and a solvent into a reaction bottle, adding hydrazine hydrate at room temperature, continuing to react for 1-2 hours, cooling, crystallizing, filtering, and drying to obtain the DL-phenylephrine.
Preferably, the solvent in the first step is dichloromethane or ethyl acetate, and the acid-binding agent is triethylamine.
Preferably, the mole ratio of m-hydroxybenzaldehyde to benzoyl chloride in step one is 1:1.0-2.0, wherein the mol ratio of m-hydroxybenzaldehyde to triethylamine is 1:1.0-3.0.
Preferably, the solvent in the second step is benzene, 2-methyltetrahydrofuran or ethyl acetate.
Preferably, the molar ratio of compound 2 to sarcosine in step two is 1:1-10, the molar ratio of compound 2 to paraformaldehyde is 1:1-10.
Preferably, the solvent in step three is ethanol or methanol.
Preferably, the molar ratio of the compound 3 to the hydrazine hydrate in the third step is 1:1.0-3.0.
Compared with the prior art, the invention has the following beneficial effects: the preparation method of DL-phenylephrine has the advantages of simple process, mild reaction conditions, wide application prospect, high purity of the obtained product and high yield.
Drawings
Other features, objects and advantages of the present application will become more apparent upon reading of the following detailed description of non-limiting embodiments thereof, made with reference to the accompanying drawings in which:
FIG. 1 is a process scheme of the present invention;
FIG. 2 is a structural formula of epinephrine of the present invention.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. The drawings are only for purposes of illustration and are not intended to be limiting, certain elements of the drawings may be omitted, enlarged or reduced to better illustrate the embodiments of the present invention, and do not represent the size of the actual product, and it is understood that some well-known structures, elements and descriptions thereof in the drawings may be omitted for persons skilled in the art.
Referring to fig. 1-2, a method for preparing DL-phenylephrine includes the following steps:
step one, adding m-hydroxybenzaldehyde (compound 1) into a reaction bottle, adding a solvent and an acid-binding agent, stirring and cooling to 0-10 ℃, dropwise adding benzoyl chloride, controlling the temperature to 0-10 ℃, stirring and reacting, adding water to extract and separate liquid after reaction, adding n-hexane, cooling and crystallizing, filtering, and drying to obtain a compound 2;
adding the compound 2 and a solvent into a reaction bottle, stirring, adding sarcosine and paraformaldehyde, heating to reflux, carrying out water diversion reaction for 3-6h, cooling after the reaction is finished, adding water, extracting, separating liquid, drying with anhydrous sodium sulfate, and concentrating under reduced pressure to obtain a compound 3;
and step three, adding the compound 3 and a solvent into a reaction bottle, adding hydrazine hydrate at room temperature, continuing to react for 1-2 hours, cooling, crystallizing, filtering, and drying to obtain the DL-phenylephrine.
Wherein the solvent in the step one is dichloromethane or ethyl acetate, and the acid-binding agent is triethylamine.
Wherein the mol ratio of m-hydroxybenzaldehyde to benzoyl chloride in the step one is 1:1.0-2.0, wherein the mol ratio of m-hydroxybenzaldehyde to triethylamine is 1:1.0-3.0.
Wherein, the solvent in the second step is benzene, 2-methyltetrahydrofuran or ethyl acetate.
Wherein the molar ratio of the compound 2 to the sarcosine in the second step is 1:1-10, the molar ratio of compound 2 to paraformaldehyde is 1:1-10.
Wherein, the solvent in the third step is ethanol or methanol.
Wherein, the molar ratio of the compound 3 to the hydrazine hydrate in the third step is 1:1.0-3.0.
It should be noted that: the preparation method of DL-phenylephrine has the advantages of simple process, mild reaction conditions and larger application prospect, and simultaneously the obtained product has high purity and high yield;
those not described in detail in this specification are within the skill of the art.
Example 1
As shown in fig. 1, the preparation method of DL-phenylephrine of the present invention comprises the following steps:
1) Dichloromethane (200 ml), m-hydroxybenzaldehyde (50 g) and triethylamine (50 g) were added to a three-necked flask, and benzoyl chloride (60 g) was added dropwise with stirring at 5 ℃ to continue the reaction for 1 hour. After the reaction was completed, water (100 ml) was added and the mixture was stirred and washed, followed by liquid separation, and the organic phase was collected and washed again with water (100 ml). Collecting an organic phase, adding n-hexane (300 ml), stirring, cooling, crystallizing, filtering, leaching a filter cake with n-hexane to obtain a white-like crystal, and performing forced air drying to obtain 52g of a compound with the yield of 56.14%.
2) Adding the compound 2 (5 g) and ethyl acetate (25 ml) into a three-neck flask, adding sarcosine (5.9 g) and paraformaldehyde (4 g) under stirring, heating to reflux under stirring, and continuing refluxing for water diversion reaction. After the reaction, water (50 ml) was added, extraction and washing were carried out with stirring, the organic phase was collected, water (50 ml) was added again, washing was carried out with stirring, the organic phase was collected, anhydrous sodium sulfate was added, drying was carried out, suction filtration was carried out, anhydrous sodium sulfate was removed, and the filtrate was concentrated under reduced pressure to obtain 5g of an oily compound with a yield of 79.84%.
3) Ethanol (30 ml) and compound 3 (2.8 g) were added to a 100ml three-necked flask, and hydrazine hydrate (1 g) was added thereto with stirring at room temperature, followed by further stirring for 1 hour. Cooling, crystallizing, filtering, leaching filter cakes with ethanol, and drying the filter cakes in vacuum to obtain 0.8g of DL-phenylephrine with the yield of 48.4 percent.
Example 2
1) Ethyl acetate (120 ml), m-hydroxybenzaldehyde (30 g) and triethylamine (30 g) were added to a reaction flask, and benzoyl chloride (36 g) was added dropwise with stirring at 5 ℃ to continue the reaction for 1 hour. And after the reaction is finished, adding 70ml of water, stirring and washing, separating liquid, collecting an organic phase, adding 70ml of water again, washing the organic phase, collecting the organic phase, adding 120ml of n-hexane, stirring, cooling, crystallizing, filtering, leaching a filter cake with the n-hexane, and drying by blowing to obtain 31g of the off-white compound with the yield of 55.78%.
2) Adding the compound 2 (5 g) and 2-methyltetrahydrofuran (25 ml) into a reaction bottle, adding sarcosine (6 g) and paraformaldehyde (3 g) with stirring, heating to reflux, and continuing the water-splitting reaction. After completion of the reaction, the reaction mixture was washed once with water (50 ml) and once with water (50 ml), and the organic phase was collected, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to give 4.8g of an oily compound in a yield of 76.7%.
3) Methanol (30 ml) and compound 3 (2.8 g) were added to a reaction flask, and hydrazine hydrate (1 g) was added thereto at room temperature with stirring, and the reaction was continued with stirring. After the reaction is finished, cooling and crystallizing, filtering, leaching a filter cake by methanol, and drying the filter cake in vacuum to obtain 0.7g of DL-phenylephrine with the yield of 42.4 percent.
It is noted that, herein, relational terms such as first and second, and the like may be used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions. Also, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus.
Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.
Claims (7)
1. A preparation method of DL-phenylephrine is characterized by comprising the following steps:
step one, adding m-hydroxybenzaldehyde (compound 1) into a reaction bottle, adding a solvent and an acid-binding agent, stirring and cooling to 0-10 ℃, dropwise adding benzoyl chloride, controlling the temperature to 0-10 ℃, stirring and reacting, adding water to extract and separate liquid after the reaction is finished, adding n-hexane, cooling and crystallizing, filtering, and drying to obtain a compound 2;
adding the compound 2 and a solvent into a reaction bottle, stirring, adding sarcosine and paraformaldehyde, heating to reflux, carrying out water diversion reaction for 3-6h, cooling after the reaction is finished, adding water, extracting, separating liquid, drying with anhydrous sodium sulfate, and concentrating under reduced pressure to obtain a compound 3;
and step three, adding the compound 3 and a solvent into a reaction bottle, adding 80% hydrazine hydrate at room temperature, continuing to react for 1-2 hours, cooling, crystallizing, filtering, and drying to obtain the DL-phenylephrine.
2. The process according to claim 1, wherein the step of preparing DL-phenylephrine comprises: in the first step, the solvent is dichloromethane or ethyl acetate, and the acid-binding agent is triethylamine.
3. The process according to claim 1, wherein the step of preparing DL-phenylephrine comprises: the mol ratio of m-hydroxybenzaldehyde to benzoyl chloride in the first step is 1:1.0-2.0, wherein the mol ratio of m-hydroxybenzaldehyde to triethylamine is 1:1.0-3.0.
4. The process according to claim 1, wherein the step of preparing DL-phenylephrine comprises: and the solvent in the second step is benzene, 2-methyltetrahydrofuran or ethyl acetate.
5. The process of claim 1, wherein the process further comprises the steps of: the molar ratio of compound 2 to sarcosine in step two is 1:1-10, the molar ratio of compound 2 to paraformaldehyde is 1:1-10.
6. The process of claim 1, wherein the process further comprises the steps of: the solvent in the third step is ethanol or methanol.
7. The process according to claim 1, wherein the step of preparing DL-phenylephrine comprises: the molar ratio of the compound 3 to the hydrazine hydrate in the third step is 1:1.0-3.0.
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| CN111689869A (en) * | 2020-06-29 | 2020-09-22 | 上海博璞诺科技发展有限公司 | Preparation method of L-phenylephrine hydrochloride |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111689869A (en) * | 2020-06-29 | 2020-09-22 | 上海博璞诺科技发展有限公司 | Preparation method of L-phenylephrine hydrochloride |
Non-Patent Citations (2)
| Title |
|---|
| VLADIMIR S. MOSHKIN，VYACHESLAV YA. SOSNOVSKIKH: "A one-pot synthesis of 4-aryl-2-methyl-1, 2, 3, 4-tetrahydro-ccarbolines from 5-aryloxazolidines and indoles via a Mannich/ Friedel–Crafts sequence", 《TETRAHEDRON LETTERS》, vol. 55, pages 6121 - 6124 * |
| VLADIMIR S. MOSHKIN，VYACHESLAV YA. SOSNOVSKIKH: "A simple two-step synthesis of 2-(alkylamino)-1-arylethanols, including racemic adrenaline, from aromatic aldehydes via 5-aryloxazolidines", 《TETRAHEDRON LETTERS》, vol. 54, pages 5869, XP028729697, DOI: 10.1016/j.tetlet.2013.08.083 * |
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