CN105348121A - Synthesis method for dihydrophenylglycine methyl ester hydrochloride - Google Patents
Synthesis method for dihydrophenylglycine methyl ester hydrochloride Download PDFInfo
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- CN105348121A CN105348121A CN201510835086.4A CN201510835086A CN105348121A CN 105348121 A CN105348121 A CN 105348121A CN 201510835086 A CN201510835086 A CN 201510835086A CN 105348121 A CN105348121 A CN 105348121A
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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
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/38—Separation; Purification; Stabilisation; Use of additives
- C07C227/40—Separation; Purification
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Abstract
The invention relates to a synthesis method for dihydrophenylglycine methyl ester hydrochloride and belongs to the technical field of medicine production. The synthesis method for the dihydrophenylglycine methyl ester hydrochloride comprises the following steps: (1) carrying out stirring; (2) carrying out catalysis; (3) carrying out a reaction; (4) carrying out primary filtration and washing; (5) carrying out secondary filtration and washing; and (6) carrying out vacuum drying and then obtaining a finished product. The synthesis method is simple, convenient and effective.
Description
Technical field
The present invention relates to medicine manufacture technology field, be specifically related to a kind of synthetic method of methyl dihydrogen benzene glycinate hydrochloride.
Background technology
Methyl dihydrogen benzene glycinate hydrochloride is a kind of pharmaceutical intermediate, of many uses; A kind of simple and easy to do synthetic method of this material demand.
Summary of the invention
Object of the present invention is to solve the problem, and provides a kind of synthetic method of simple and effective methyl dihydrogen benzene glycinate hydrochloride.
The technical scheme that the present invention solves the problem is as follows:
A synthetic method for methyl dihydrogen benzene glycinate hydrochloride, comprises the steps:
1. stir: the temperature controlling reaction vessel with cold salt bath is-6--3 DEG C, and the air excluded with rare gas element in reaction vessel, two for portion (massfraction) hydrogen phenylglycine is joined in reaction vessel, 2.6-2.7 part methyl alcohol is added again in reaction vessel, stir 8-12 minute, the temperature of the cold salt bath of rear adjustment is to-3-0 DEG C;
2. catalysis: carry out step 1. while, in reaction vessel, drip the catalyzer of 0.9-1 part with constant voltage drop-burette, and catalyzer evenly dripped until drip off in 60-80 minutes section, drip off rear continuations stirring 25-35 minute;
3. react: reaction vessel be heated to 55-65 DEG C and be incubated 160-200 minute, in backward reaction vessel, adding 0.02-0.04 part gac, continue to stir 25-35 minute;
4. first filtration washing: by step 3. in reacting liquor while hot filter, and with pair hydrogen phenylglycine washing leaching cake, to be spin-dried for rotavapor under vacuum after washings and filtrate merge;
5. secondary filtration washing: add 3.5-3.6 part methylcarbonate to step being spin-dried in thing 4., stirs 25-35 minute, is cooled to 10-30 degree Celsius, washs after filtration with 0.65-0.75 part methylcarbonate again;
6. vacuum-drying: step filter cake vacuum-drying at 55-65 DEG C is 5. obtained finished product.
Preferred as technique scheme, 1. step is: the temperature controlling reaction vessel with cold salt bath is-5 DEG C, and the air excluded with rare gas element in reaction vessel, two for portion (massfraction) hydrogen phenylglycine is joined in reaction vessel, 2.64 parts of methyl alcohol are added again in reaction vessel, stir 10 minutes, the temperature to 0 DEG C of the cold salt bath of rear adjustment.
Preferred as technique scheme, 2. step is: carry out step 1. while, in reaction vessel, drip the catalyzer of 0.93 part with constant voltage drop-burette, and catalyzer is evenly dripped until drip off in 70 minutes sections, drip off rear continuation stirring 30 minutes.
Preferred as technique scheme, step 2. in used catalyst be thionyl chloride.
Preferred as technique scheme, 3. step is: reaction vessel be heated to 60 DEG C and be incubated 180 minutes, adds 0.03 part of gac in backward reaction vessel, continues stirring 30 minutes.
Preferred as technique scheme, 5. step is: add 3.56 parts of methylcarbonates to step being spin-dried in thing 4., stir 30 minutes, be cooled to 20 degrees Celsius, wash after filtration with 0.71 part of methylcarbonate again.
Preferred as technique scheme, 6. step is: step filter cake vacuum-drying at 60 DEG C is 5. obtained finished product.
In sum, the present invention has following beneficial effect:
The simple synthetic method of a kind of methyl dihydrogen benzene glycinate hydrochloride of the present invention is easy and effective.
Accompanying drawing explanation
Fig. 1 is the synthetic method craft schema of methyl dihydrogen benzene glycinate hydrochloride.
Embodiment
Be clearly and completely described to the technical scheme in the embodiment of the present invention below, obviously, described embodiment is only the present invention's part embodiment, instead of whole embodiments.Embodiment in the present invention, those of ordinary skill in the art, not doing other embodiments all obtained under creative work prerequisite, belong to the scope of protection of the invention.
Below in conjunction with accompanying drawing, with embodiment, the present invention is described in detail.
Embodiment 1: a kind of synthetic method of methyl dihydrogen benzene glycinate hydrochloride, comprises the steps:
1. stir: the temperature controlling reaction vessel with cold salt bath is-6 DEG C, and the air excluded with rare gas element in reaction vessel, two for portion (massfraction) hydrogen phenylglycine is joined in reaction vessel, 2.6 parts of methyl alcohol are added again in reaction vessel, stir 8 minutes, the temperature of the cold salt bath of rear adjustment is to-3 DEG C;
2. catalysis: carry out step 1. while, in reaction vessel, drip the catalyzer of 0.9 part with constant voltage drop-burette, and catalyzer evenly dripped until drip off in 60 minutes sections, drip off rear continuation stirring 25 minutes;
3. react: reaction vessel be heated to 55 DEG C and be incubated 160 minutes, in backward reaction vessel, adding 0.02 part of gac, continue stirring 25 minutes;
4. first filtration washing: by step 3. in reacting liquor while hot filter, and with pair hydrogen phenylglycine washing leaching cake, to be spin-dried for rotavapor under vacuum after washings and filtrate merge;
5. secondary filtration washing: add 3.5 parts of methylcarbonates to step being spin-dried in thing 4., stir 25 minutes, be cooled to 10 degrees Celsius, wash with 0.65 part of methylcarbonate again after filtration;
6. vacuum-drying: step filter cake vacuum-drying at 55 DEG C is 5. obtained finished product.
Embodiment 2: a kind of synthetic method of methyl dihydrogen benzene glycinate hydrochloride, comprises the steps:
1. stir: the temperature controlling reaction vessel with cold salt bath is-3 DEG C, and the air excluded with rare gas element in reaction vessel, two for portion (massfraction) hydrogen phenylglycine is joined in reaction vessel, 2.7 parts of methyl alcohol are added again in reaction vessel, stir 12 minutes, the temperature to 0 DEG C of the cold salt bath of rear adjustment;
2. catalysis: carry out step 1. while, in reaction vessel, drip the catalyzer of 1 part with constant voltage drop-burette, and catalyzer evenly dripped until drip off in 80 minutes sections, drip off rear continuation stirring 35 minutes;
3. react: reaction vessel be heated to 65 DEG C and be incubated 200 minutes, in backward reaction vessel, adding 0.04 part of gac, continue stirring 35 minutes;
4. first filtration washing: by step 3. in reacting liquor while hot filter, and with pair hydrogen phenylglycine washing leaching cake, to be spin-dried for rotavapor under vacuum after washings and filtrate merge;
5. secondary filtration washing: add 3.6 parts of methylcarbonates to step being spin-dried in thing 4., stir 35 minutes, be cooled to 30 degrees Celsius, wash with 0.75 part of methylcarbonate again after filtration;
6. vacuum-drying: step filter cake vacuum-drying at 65 DEG C is 5. obtained finished product.
Embodiment 3: a kind of synthetic method of methyl dihydrogen benzene glycinate hydrochloride, comprises the steps:
1. stir: the temperature controlling reaction vessel with cold salt bath is-5 DEG C, and the air excluded with rare gas element in reaction vessel, two for portion (massfraction) hydrogen phenylglycine is joined in reaction vessel, 2.64 parts of methyl alcohol are added again in reaction vessel, stir 10 minutes, the temperature to 0 DEG C of the cold salt bath of rear adjustment;
2. catalysis: carry out step 1. while, in reaction vessel, drip the catalyzer of 0.93 part with constant voltage drop-burette, and catalyzer evenly dripped until drip off in 70 minutes sections, drip off rear continuation stirring 30 minutes;
3. react: reaction vessel be heated to 60 DEG C and be incubated 180 minutes, in backward reaction vessel, adding 0.03 part of gac, continue stirring 30 minutes;
4. first filtration washing: by step 3. in reacting liquor while hot filter, and with pair hydrogen phenylglycine washing leaching cake, to be spin-dried for rotavapor under vacuum after washings and filtrate merge;
5. secondary filtration washing: add 3.56 parts of methylcarbonates to step being spin-dried in thing 4., stir 30 minutes, be cooled to 20 degrees Celsius, wash with 0.71 part of methylcarbonate again after filtration;
6. vacuum-drying: step filter cake vacuum-drying at 60 DEG C is 5. obtained finished product.
Claims (7)
1. a synthetic method for methyl dihydrogen benzene glycinate hydrochloride, is characterized in that: comprise the steps:
1. stir: the temperature controlling reaction vessel with cold salt bath is-6--3 DEG C, and the air excluded with rare gas element in reaction vessel, two for portion (massfraction) hydrogen phenylglycine is joined in reaction vessel, 2.6-2.7 part methyl alcohol is added again in reaction vessel, stir 8-12 minute, the temperature of the cold salt bath of rear adjustment is to-3-0 DEG C;
2. catalysis: carry out step 1. while, in reaction vessel, drip the catalyzer of 0.9-1 part with constant voltage drop-burette, and catalyzer evenly dripped until drip off in 60-80 minutes section, drip off rear continuations stirring 25-35 minute;
3. react: reaction vessel be heated to 55-65 DEG C and be incubated 160-200 minute, in backward reaction vessel, adding 0.02-0.04 part gac, continue to stir 25-35 minute;
4. first filtration washing: by step 3. in reacting liquor while hot filter, and with pair hydrogen phenylglycine washing leaching cake, to be spin-dried for rotavapor under vacuum after washings and filtrate merge;
5. secondary filtration washing: add 3.5-3.6 part methylcarbonate to step being spin-dried in thing 4., stirs 25-35 minute, is cooled to 10-30 degree Celsius, washs after filtration with 0.65-0.75 part methylcarbonate again;
6. vacuum-drying: step filter cake vacuum-drying at 55-65 DEG C is 5. obtained finished product.
2. the synthetic method of a kind of methyl dihydrogen benzene glycinate hydrochloride according to claim 1, it is characterized in that: 1. step is: the temperature controlling reaction vessel with cold salt bath is-5 DEG C, and the air excluded with rare gas element in reaction vessel, two for portion (massfraction) hydrogen phenylglycine is joined in reaction vessel, 2.64 parts of methyl alcohol are added again in reaction vessel, stir 10 minutes, the temperature to 0 DEG C of the cold salt bath of rear adjustment.
3. the synthetic method of a kind of methyl dihydrogen benzene glycinate hydrochloride according to claim 1, it is characterized in that: 2. step is: carry out step 1. while, in reaction vessel, the catalyzer of 0.93 part is dripped with constant voltage drop-burette, and catalyzer is evenly dripped until drip off in 70 minutes sections, drip off rear continuation stirring 30 minutes.
4. the synthetic method of a kind of methyl dihydrogen benzene glycinate hydrochloride according to claim 1, is characterized in that: step 2. middle used catalyst is thionyl chloride.
5. the synthetic method of a kind of methyl dihydrogen benzene glycinate hydrochloride according to claim 1, it is characterized in that: 3. step is: reaction vessel be heated to 60 DEG C and be incubated 180 minutes, add 0.03 part of gac in backward reaction vessel, continue stirring 30 minutes.
6. the synthetic method of a kind of methyl dihydrogen benzene glycinate hydrochloride according to claim 1, it is characterized in that: 5. step is: add 3.56 parts of methylcarbonates to step being spin-dried in thing 4., stir 30 minutes, be cooled to 20 degrees Celsius, wash with 0.71 part of methylcarbonate again after filtration.
7. the synthetic method of a kind of methyl dihydrogen benzene glycinate hydrochloride according to claim 1, is characterized in that: 6. step is: step filter cake vacuum-drying at 60 DEG C is 5. obtained finished product.
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| CN201510835086.4A CN105348121A (en) | 2015-11-26 | 2015-11-26 | Synthesis method for dihydrophenylglycine methyl ester hydrochloride |
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| CN201510835086.4A CN105348121A (en) | 2015-11-26 | 2015-11-26 | Synthesis method for dihydrophenylglycine methyl ester hydrochloride |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3978034A (en) * | 1969-11-12 | 1976-08-31 | E. R. Squibb & Sons, Inc. | L-Aspartyl dipeptides as sweetening agents |
| CN1986823A (en) * | 2006-12-27 | 2007-06-27 | 浙江昂利康制药有限公司 | Cefradine preparing process |
| CN103665000A (en) * | 2013-11-07 | 2014-03-26 | 广州白云山制药股份有限公司广州白云山化学制药厂 | Preparation method and another use of cephalosporin |
| CN103833772A (en) * | 2014-02-28 | 2014-06-04 | 广州白云山制药股份有限公司广州白云山化学制药厂 | Method for synthesizing cephalosporin |
-
2015
- 2015-11-26 CN CN201510835086.4A patent/CN105348121A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3978034A (en) * | 1969-11-12 | 1976-08-31 | E. R. Squibb & Sons, Inc. | L-Aspartyl dipeptides as sweetening agents |
| CN1986823A (en) * | 2006-12-27 | 2007-06-27 | 浙江昂利康制药有限公司 | Cefradine preparing process |
| CN103665000A (en) * | 2013-11-07 | 2014-03-26 | 广州白云山制药股份有限公司广州白云山化学制药厂 | Preparation method and another use of cephalosporin |
| CN103833772A (en) * | 2014-02-28 | 2014-06-04 | 广州白云山制药股份有限公司广州白云山化学制药厂 | Method for synthesizing cephalosporin |
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