CN106905177A - A kind of preparation method of the biphenyl propionic acid ethyl ester derivative hydrochloride of 2 amino 3 - Google Patents
A kind of preparation method of the biphenyl propionic acid ethyl ester derivative hydrochloride of 2 amino 3 Download PDFInfo
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- CN106905177A CN106905177A CN201710013415.6A CN201710013415A CN106905177A CN 106905177 A CN106905177 A CN 106905177A CN 201710013415 A CN201710013415 A CN 201710013415A CN 106905177 A CN106905177 A CN 106905177A
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- biphenyl
- amino
- ethyl ester
- propionic acid
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/18—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
- C07C17/10—Preparation of halogenated hydrocarbons by replacement by halogens of hydrogen atoms
- C07C17/14—Preparation of halogenated hydrocarbons by replacement by halogens of hydrogen atoms in the side-chain of aromatic compounds
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/68—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton
- C07C209/74—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton by halogenation, hydrohalogenation, dehalogenation, or dehydrohalogenation
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/11—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by reactions increasing the number of carbon atoms
- C07C37/20—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by reactions increasing the number of carbon atoms using aldehydes or ketones
Abstract
The invention belongs to fine chemistry industry or pharmaceutical intermediate preparing technical field, and in particular to a kind of preparation method of the biphenyl propionic acid ethyl ester derivative hydrochloride of 2 amino 3.First with biphenyl derivatives as raw material, by chloromethylation, 4 chloromethyl biphenyl derivatives are obtained, then by substitution reaction, obtain the biphenyl propionic acid ethyl ester derivative hydrochloride of 2 amino of target product 3.Compared with prior art, beneficial effects of the present invention are：Reaction scheme is short, and the material variety for using is few, and operation is relatively easy, and without HTHP demand, energy consumption is low, low cost, the high income of the target product for obtaining, quality better, therefore the preparation method is appropriate for producing in enormous quantities, with preferable application prospect.
Description
Technical field
The invention belongs to fine chemistry industry or pharmaceutical intermediate preparing technical field, and in particular to a kind of 2- amino -3- biphenyl
The preparation method of base ethyl propionate derivant hydrochloric acid salt.
Background technology
2- amino -3- biphenyl propionic acid ethyl ester derivative hydrochlorides of the invention are the keys of cardiotonic agents AHU-377
Intermediate, while prepared intermediate product biphenyl derivatives are widely used in the fields such as medicine, chemical industry, material, liquid crystal, there is wide
Wealthy application prospect.There is reagent selection in the 2- amino -3- biphenyl propionic acid ethyl ester derivative hydrochlorides reported in prior art
Property it is not high, reaction scheme is more long, and material used and reagent are more, operates relatively complicated, and relatively costly, yield is relatively low, and (65% is left
It is right) etc. deficiency, therefore its economy and practicality be not high.Therefore, lack in the prior art a kind of reaction scheme it is relatively short, operation
Simply, yield is high and 2- amino -3- biphenyl propionic acids ethyl ester derivative hydrochloric acid salt production process of low cost.
The content of the invention
The technical problems to be solved by the invention are to provide a kind of 2- amino -3- biphenyl propionic acid ethyl ester derivative hydrochloric acid
Salt, its reaction scheme is relatively short, simple to operate, yield is high and low cost.
The technical scheme that the present invention solves above-mentioned technical problem is as follows：A kind of 2- amino -3- biphenyl propionic acids ethyl ester derives
The preparation method of thing hydrochloride, it comprises the following steps：
S1. with biphenyl derivatives, paraformaldehyde, HCl gases are dried as raw material, under catalyst action, by chloromethyl
Change reaction and prepare 4- chloromethylbenzene derivatives；
S2. by N- (diphenylmethyl alkenyl) ethyl aminoacetates and 4- chloromethylbenzene derivatives according to 1-3:1 mol ratio
It is dissolved in organic solvent and obtains reaction solution, at -5-10 DEG C, aqueous slkali is added dropwise makes reaction solution be in alkaline, insulation reaction 5-8h to temperature control, then
Hydrochloric acid is directly added dropwise in reaction solution, makes reaction solution in acidity, at -5-10 DEG C, insulation reaction 5-8h stands temperature control, and point liquid is dense
It is reduced to dry, obtains pulverulent solids, as described 2- amino -3- biphenyl propionic acid ethyl ester derivative hydrochlorides.
The reaction scheme of above-mentioned preparation method is as follows：
Compound 1 is target product 2- amino -3- biphenyl propionic acid ethyl ester derivative hydrochlorides in above-mentioned reaction scheme
Structural formula, compound 2 is biphenyl derivatives, and compound 3 is the product 4- chloromethylbenzene derivatives of step S1.
On the basis of above-mentioned preparation method, the present invention can also have following further specifically chosen：
Specifically, the biphenyl derivatives in S1 are any in biphenyl, 4- aminobphenyls, 4- xenols and 4- chlordiphenyls
Kind.
Specifically, the biphenyl derivatives and the mol ratio of paraformaldehyde in S1 are 1：1.2-4, biphenyl derivatives and drying
The mol ratio of HCl gases is 1：0.5-1.5.
Specifically, the catalyst in S1 is any one in zinc chloride, aluminium chloride, iron chloride and boron trifluoride.
Specifically, biphenyl derivatives and the mol ratio of catalyst are 1 in S1：3.
Specifically, the organic solvent in S2 is DMF, DMA and N- methylpyrroles
Any one in alkanone.
Specifically, 4- chloromethylbenzenes derivative and the amount ratio of organic solvent are 1mmol in S2:1-1.5mL.
Specifically, it is sodium hydroxide solution, potassium hydroxide solution, the carbon of 20-25% that the aqueous slkali in S2 is mass fraction
Acid sodium solution or solution of potassium carbonate.
Preferably, NaOH contained by the aqueous slkali in the reaction solution, potassium hydroxide, sodium carbonate or carbon are instilled in S2
Sour potassium is 1.5-2.5 with the mol ratio of 4- chloromethylbenzene derivatives：1.
Specifically, the mass fraction that the hydrochloric acid in the reaction solution is instilled in S2 is 10-15%, HCl in the hydrochloric acid of instillation
It is 8.5-13.2 with the mol ratio of 4- chloromethylbenzene derivatives：1.
Relative to prior art, the beneficial effects of the invention are as follows：
It prepares 4- chloromethyl biphenyl derivatives by chloromethylation first with biphenyl derivatives as raw material,
Then carry out substitution reaction with N- (diphenylmethyl alkenyl) ethyl aminoacetate and obtain target product, its reaction scheme is short, uses
Material variety it is few, operate it is relatively easy, without HTHP demand, energy consumption is low, low cost, the yield of the target product for obtaining
High, quality better, therefore the preparation method is appropriate for producing in enormous quantities, with preferable application prospect.
Specific embodiment
Principle of the invention and feature are described below in conjunction with specific embodiment, example is served only for explaining this hair
It is bright, it is not intended to limit the scope of the present invention.
Medicine used in following examples, is commercially available prod unless otherwise noted, and the method for being used (is such as divided
Liquid, filtering, drying, temperature control etc.) conventional method is unless otherwise noted.
The reaction scheme of the preparation method that the present invention is provided is as follows：
Compound 1 is target product 2- amino -3- biphenyl propionic acid ethyl ester derivative hydrochlorides in above-mentioned reaction scheme
Structural formula, compound 2 is biphenyl derivatives, and compound 3 is the product 4- chloromethylbenzene derivatives of step S1.
Embodiment 1
In reaction bulb, biphenyl (100mmol), the paraformaldehyde (200mmol) of 6.0g of 15.4g are added, it is possible to additionally incorporate
The iron chloride (300mmol) of 48.5g, four-hole bottle bottom is passed through by wireway, opens HCl gas generating units, is slowly introducing dry
Dry HC1 gases (100mmol), 70~80 DEG C of temperature control reacts 18h.Cooling, by reaction solution addition frozen water, uses ethyl acetate
Extraction three times, merges organic layer, uses saturation NaHCO3Solution removes ethyl acetate, obtains white solid, second with neutrality, distillation is washed to
Alcohol is recrystallized, and obtains 16.2g off-white colors or white powder 4- chloromethyl biphenyls (compound 3, R=-H, yield 80.2%, m.p:71
~73 DEG C).
In reaction bulb, 4- chloromethyl biphenyls (100mmo1), N- (diphenylmethyl alkenyl) ammonia of 29.4g of 20.2g is added
The DMF (DMF) of ethyl (110mmol) and 140mL, temperature control is slowly dropped at -5~10 DEG C
20%KOH solution (11.2g containing KOH, 199.6mmo1), is incubated 5h.Then directly in reaction solution, 10% hydrochloric acid is instilled
300mL (HCl0.85mol), -5~10 DEG C of insulation 5h, stands, and be concentrated to dryness for organic solvent by branch vibration layer, obtains 28.8g yellowish
Color powder 2- amino -3- (4- xenyls)-propionate hydrochloride (compound 1, R=-H, yield 94.5%).FAB-MS(m/
z)：292[M+H]+；FT-IR (KBr compressing tablets, σ cm-1)：3158,1698,1621,1567.
Embodiment 2
In reaction bulb, 4- aminobphenyls (100mmol), the paraformaldehyde (200mmol) of 6.0g of 16.9g are added, separately
Aluminum trichloride (anhydrous) (300mmol), the 1-METHYLPYRROLIDONE of 100mL, the dimethyl sulfoxide of 5g of outer addition 40g, by wireway
Four-hole bottle bottom is passed through, HCl gas generating units are opened, HC1 gases (150mmol), 70~90 DEG C of temperature control, reaction is slowly introducing
16h.Cooling, by reaction solution addition frozen water, is extracted with ethyl acetate three times, merges organic layer, uses saturation NaHCO3Solution and
Neutrality is washed to, distillation removes ethyl acetate, obtains white solid, and ethyl alcohol recrystallization obtains 17.8g pale yellow powder 4'- amino -4- chlorine
Methyl biphenyl (compound 3, R=-NH2, yield 81.3%).
In reaction bulb, 4'- amino -4- chloromethyl biphenyls (100mmo1), the N- (diphenyl of 29.4g of 21.9g are added
Methene) ethyl aminoacetate (110mmol) and 140mL DMF (DMF), temperature control at -5~10 DEG C,
20%KOH solution (containing KOH11.2g, 199.6mmo1) is slowly dropped into, 5h is incubated.Then directly in reaction solution, 10% is instilled
Hydrochloric acid 300mL (HCl0.85mol), -5~10 DEG C of insulation 5h, stands, and be concentrated to dryness for organic solvent by branch vibration layer, obtains 24.3g
Pale yellow powder 2- amino -3- (4- Amino-biphenyls)-propionate hydrochloride (compound 1, R=-NH2, yield
79.2%).FAB-MS(m/z)：308[M+H]+；FT-IR (KBr compressing tablets, σ cm-1)：3126,1726,1606,1544.
Embodiment 3
In reaction bulb, 4- xenols (100mmol), the paraformaldehyde (300mmol) of 9.0g of 17.0g are added, separately
Zinc chloride (300mmol), the 1-METHYLPYRROLIDONE of 100mL, the dimethyl sulfoxide of 8g of outer addition 40.8g, wireway is passed through
Four-hole bottle bottom, opens HCl gas generating units, is slowly introducing dry HC1 gases (50mmol), 80~100 DEG C of temperature control, instead
Answer 18h.Cooling, by reaction solution addition frozen water, is extracted with ethyl acetate three times, merges organic layer, uses saturation NaHCO3Solution
Be washed to neutrality, distillation removes ethyl acetate, obtains white solid, recrystallisation from isopropanol, obtain 16.8g field gray powder 4'- hydroxyls-
4- chloromethyl biphenyls (compound 3, R=-OH, yield 76.4%).
In reaction bulb, 4'- hydroxyl -4- chloromethyl biphenyls (100mmo1), the N- (diphenyl of 29.4g of 22.0g are added
Methene) ethyl aminoacetate (110mmol) and 140mL DMA (DMA), temperature control at -5~15 DEG C,
20%NaOH solution is slowly dropped into, 6h is incubated.Then directly in reaction solution, 15% hydrochloric acid 300mL (HCl are instilled
1.32mol), -5~15 DEG C of insulation 6h, stand, and be concentrated to dryness for organic solvent by branch vibration layer, obtains 23.9g buff powder 2-
Amino -3- (4- Hydroxy-biphenyls)-propionate hydrochloride (compound 1, R=-OH, yield 77.7%).FAB-MS(m/z)：
309[M+H]+；FT-IR (KBr compressing tablets, σ cm-1)：3222,3345,1689,1651,1523.
Embodiment 4
In reaction bulb, 4- chlordiphenyls (100mmol), the paraformaldehyde (300mmol) of 9.0g of 18.9g are added, in addition
Zinc chloride (300mmol), the hexamethylene of 100mL, the dimethyl sulfoxide of 8g of 40.8g are added, wireway are passed through four-hole bottle bottom,
HCl gas generating units are opened, dry HC1 gases (80mmol) are slowly introducing, 80~100 DEG C of temperature control reacts 18h.Cooling,
By in reaction solution addition frozen water, it is extracted with ethyl acetate three times, merges organic layer, uses saturation NaHCO3Solution and it is washed to
Property, distill and remove ethyl acetate, white solid is obtained, recrystallisation from isopropanol obtains the 17.7g buff powder chloro- 4- chloromethyl biphenyls of 4'-
(compound 3, R=-Cl, yield 78.9%).
In reaction bulb, the chloro- 4- chloromethyl biphenyls (100mmo1) of 4'-, the N- (diphenylmethyls of 34.7g of 22.4g are added
Alkenyl) ethyl aminoacetate (130mmol) and 150mL DMA (DMA), temperature control delays at -5~10 DEG C
It is slow to instill 20%NaOH solution, it is incubated 8h.Then directly in reaction solution, 15% hydrochloric acid 300mL (HCl 1.32mol) is instilled ,-
5~10 DEG C of insulation 8h, stand, and be concentrated to dryness for organic solvent by branch vibration layer, obtains 24.6g pale yellow powder 2- amino -3- (4-
Chloro- xenyl)-propionate hydrochloride (compound 1, R=-Cl, yield 75.4%).FAB-MS(m/z)：328[M+H]+；
FT-IR (KBr compressing tablets, σ cm-1)：3252,3248,1716,1645,1511.
Yield, fast atom bombardment mass spectroscopy (FAB-MS), the infrared spectrum (FT- of the target product prepared by above-described embodiment
) etc. IR data understand that the preparation method provided by the present invention can be obtained target product 2- amino -3- biphenyl propionic acid ethyl esters and spread out
Biological hydrochloride and its yield is more than 75%, hence it is evident that the yield higher than in the prior art 65% or so.
The foregoing is only presently preferred embodiments of the present invention, be not intended to limit the invention, it is all it is of the invention spirit and
Within principle, any modification, equivalent substitution and improvements made etc. should be included within the scope of the present invention.
Claims (10)
1. a kind of preparation method of 2- amino -3- biphenyl propionic acid ethyl ester derivative hydrochlorides, it is characterised in that including following step
Suddenly：
S1. with biphenyl derivatives, paraformaldehyde, dry HCl gases as raw material, it is anti-by chloromethylation under catalyst action
4- chloromethylbenzene derivatives should be prepared；
S2. the 4- chloromethylbenzene derivatives for preparing N- (diphenylmethyl alkenyl) ethyl aminoacetates and S1 are according to 1-3:1 rubs
You obtain reaction solution than being dissolved in organic solvent, and at -5-10 DEG C, aqueous slkali is added dropwise makes reaction solution in alkaline, insulation reaction 5-8h to temperature control,
Then hydrochloric acid is directly added dropwise in reaction solution, makes reaction solution in acidity, at -5-10 DEG C, insulation reaction 5-8h stands temperature control, point
Liquid, is concentrated to dryness, and obtains pulverulent solids, as described 2- amino -3- biphenyl propionic acid ethyl ester derivative hydrochlorides.
2. the preparation method of a kind of 2- amino -3- biphenyl propionic acid ethyl ester derivative hydrochlorides according to claim 1, its
It is characterised by, the biphenyl derivatives in S1 are any one in biphenyl, 4- aminobphenyls, 4- xenols and 4- chlordiphenyls.
3. the preparation method of a kind of 2- amino -3- biphenyl propionic acid ethyl ester derivative hydrochlorides according to claim 2, its
It is characterised by, the biphenyl derivatives in S1 are 1 with the mol ratio of paraformaldehyde：1.2-4, biphenyl derivatives with dry HCl gases
Mol ratio be 1：0.5-1.5.
4. the preparation method of a kind of 2- amino -3- biphenyl propionic acid ethyl ester derivative hydrochlorides according to claim 2, its
It is characterised by, the catalyst in S1 is any one in zinc chloride, aluminium chloride, iron chloride and boron trifluoride.
5. the preparation method of a kind of 2- amino -3- biphenyl propionic acid ethyl ester derivative hydrochlorides according to claim 4, its
It is characterised by, biphenyl derivatives and the mol ratio of catalyst are 1 in S1：3.
6. the preparation method of a kind of 2- amino -3- biphenyl propionic acid ethyl ester derivative hydrochlorides according to claim 1, its
It is characterised by, the organic solvent in S2 is in DMF, DMA and 1-METHYLPYRROLIDONE
Any one.
7. the preparation method of a kind of 2- amino -3- biphenyl propionic acid ethyl ester derivative hydrochlorides according to claim 1, its
It is characterised by, 4- chloromethylbenzenes derivative and the amount ratio of organic solvent are 1mmol in S2:1-1.5mL.
8. the preparation method of a kind of 2- amino -3- biphenyl propionic acid ethyl ester derivative hydrochlorides according to claim 1, its
It is characterised by, the aqueous slkali in S2 is mass fraction for the sodium hydroxide solution of 20-25%, potassium hydroxide solution, sodium carbonate are molten
Liquid or solution of potassium carbonate.
9. the preparation method of a kind of 2- amino -3- biphenyl propionic acid ethyl ester derivative hydrochlorides according to claim 8, its
Be characterised by, instilled in S2 NaOH contained by the aqueous slkali in the reaction solution, potassium hydroxide, sodium carbonate or potassium carbonate with
The mol ratio of 4- chloromethylbenzene derivatives is 1.5-2.5：1.
10. a kind of 2- amino -3- biphenyl propionic acid ethyl ester derivative hydrochlorides according to any one of claim 1 to 9
Preparation method, it is characterised in that the mass fraction that the hydrochloric acid in the reaction solution is instilled in S2 is 10-15%, the hydrochloric acid of instillation
Middle HCl is 8.5-13.2 with the mol ratio of 4- chloromethylbenzene derivatives：1.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110128284A (en) * | 2019-06-13 | 2019-08-16 | 南京一心和医药科技有限公司 | A kind of preparation method of 2- amino -3- biphenyl propionic acid |
| CN111574354A (en) * | 2020-06-18 | 2020-08-25 | 安徽鼎旺医药有限公司 | Biphenylacetic acid and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101830853A (en) * | 2010-04-23 | 2010-09-15 | 武汉工程大学 | Nitroimidazoline derivatives and preparation method thereof and application thereof |
| CN105168205A (en) * | 2015-08-18 | 2015-12-23 | 泰力特医药（湖北）有限公司 | Preparation method for dual inhibitor LCZ696 of angiotensin II receptor and neprilysin |
-
2017
- 2017-01-09 CN CN201710013415.6A patent/CN106905177A/en not_active Withdrawn
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101830853A (en) * | 2010-04-23 | 2010-09-15 | 武汉工程大学 | Nitroimidazoline derivatives and preparation method thereof and application thereof |
| CN105168205A (en) * | 2015-08-18 | 2015-12-23 | 泰力特医药（湖北）有限公司 | Preparation method for dual inhibitor LCZ696 of angiotensin II receptor and neprilysin |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110128284A (en) * | 2019-06-13 | 2019-08-16 | 南京一心和医药科技有限公司 | A kind of preparation method of 2- amino -3- biphenyl propionic acid |
| CN110128284B (en) * | 2019-06-13 | 2021-12-14 | 南京一心和医药科技有限公司 | Preparation method of 2-amino-3-biphenylyl propionic acid |
| CN111574354A (en) * | 2020-06-18 | 2020-08-25 | 安徽鼎旺医药有限公司 | Biphenylacetic acid and preparation method thereof |
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