CN106986834B - The preparation method of 5- ethyl -5- (1- methyl butyl) barbiturates sodium - Google Patents
The preparation method of 5- ethyl -5- (1- methyl butyl) barbiturates sodium Download PDFInfo
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- CN106986834B CN106986834B CN201710386429.2A CN201710386429A CN106986834B CN 106986834 B CN106986834 B CN 106986834B CN 201710386429 A CN201710386429 A CN 201710386429A CN 106986834 B CN106986834 B CN 106986834B
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- ethyl
- methyl butyl
- sodium
- barbiturates
- malonyl urea
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/60—Three or more oxygen or sulfur atoms
- C07D239/62—Barbituric acids
Abstract
The invention belongs to pharmaceutical preparation fields, more particularly to it is a kind of prepare for calmness, hypnosis, preanesthetic medication and anticonvulsant drug 5- ethyl -5- (1- methyl butyl) barbiturates sodium preparation method, use 5- ethyl -5- (1- methyl butyl) malonyl urea compound for raw material, which includes two steps: A, 5- ethyl -5- (1- methyl butyl) malonyl urea acts on the wet product that 5- ethyl -5- (1- methyl butyl) barbiturates sodium is made in acetone soln with the methanol solution of sodium methoxide；B, by the vacuum dried finished product for obtaining 5- ethyl -5- (1- methyl butyl) barbiturates sodium of the wet product of 5- ethyl -5- (1- methyl butyl) barbiturates sodium obtained above.The process stabilizing, easy to operate, with short production cycle, good product quality, purity is high, high income, production cost is low, and low energy consumption, and disposing mother liquor recycles, and the three wastes are few, is suitble to industrialized production.
Description
Technical field
The invention belongs to pharmaceutical preparation fields, and in particular to the preparation of 5- ethyl -5- (1- methyl butyl) barbiturates sodium
Method.
Background technique
5- ethyl -5- (1- methyl butyl) barbiturates sodium belongs to calmness, hypnosis, preanesthetic medication and anticonvulsant drug.
The paper " synthesising process research of yellow Jackets " of " chemical reagent " (2011,33 (9), 857~858) report, synthesis side
Method is that 4.4g (0.11mol) sodium hydroxide is dissolved in 40mL dehydrated alcohol, and filtering removes insoluble matter, and 22.6g is added
(0.1mol) amobarbital, heating make it dissolve, and control interior temperature and are no more than 50 DEG C, pH value of solution adds active carbon 9.0~9.5
Decolourize 30min, after filtering out active carbon, ethyl alcohol is concentrated under filtrate decompression, acetone is added to nodeless mesh in gained residue under stiring
It being precipitated, filter collection solid, a small amount of dehydrated alcohol washs 1 time, and anhydrous ether washs 1 time, dry product 20.6g, yield 83.0%,
MP:126~128 DEG C.And sodium hydroxide used in this method is initially dissolved in dehydrated alcohol and adds 5- ethyl-through filtering
5- (1- methyl butyl) malonyl urea it is heated dissolution, decoloration, filtering, concentration etc. operating procedures, finally add acetone crystallization,
Filter collection solid, and is washed respectively with dehydrated alcohol and anhydrous ether, through dry 5- ethyl -5- (1- methyl butyl) barbiturates
Sodium.
The disadvantages of the method are as follows technical process is complicated for operation, product yield is low, low efficiency, and energy consumption is high, and uses more
Kind solvent mixing is difficult to recycle, and there are safety hazard height, the three wastes are more, at high cost.
Summary of the invention
In view of the deficiencies of the prior art, 5- ethyl -5- (1- methyl butyl) bar is prepared the object of the present invention is to provide a kind of
Than the new process of appropriate sour sodium, the process stabilizing, reaction condition is easily controllable, and easy to operate, low energy consumption, the three wastes are few, products obtained therefrom
High-quality (HPLC purity > 99.8%), high income, production cost is low, is more suitable for industrialized production.
The object of the present invention is achieved like this:
The preparation method of 5- ethyl -5- (1- methyl butyl) barbiturates sodium, it is characterised in that: this method includes two steps
It is rapid:
A, 5- ethyl -5- (1- methyl butyl) malonyl urea is made in acetone soln with the effect of the methanol solution of sodium methoxide
The wet product of 5- ethyl -5- (1- methyl butyl) barbiturates sodium；
B, by the above-mentioned wet product for obtaining 5- ethyl -5- (1- methyl butyl) barbiturates sodium it is vacuum dried 5- ethyl -
The finished product of 5- (1- methyl butyl) barbiturates sodium.
Concrete operations technique are as follows:
In acetone by the dissolution of 5- ethyl -5- (1- methyl butyl) malonyl urea, insoluble matter impurity is removed by filtration, is made
The acetone soln of 5- ethyl -5- (1- methyl butyl) malonyl urea.The methanol of filtered sodium methoxide is slowly added dropwise under stiring
Solution, it is crystallized, it is filtered, washed, is dried in vacuo the new process for preparing 5- ethyl -5- (1- methyl butyl) barbiturates sodium.Its
It reacts as follows:
Wherein, mass ratio=1:5~10 of 5- ethyl -5- (1- methyl butyl) malonyl urea and solvent acetone；5- ethyl-
Molar ratio=1:1.05~1.1 of sodium methoxide in 5- (1- methyl butyl) malonyl urea and methanol solution of sodium methylate.Reaction be
It completes at room temperature, the dropwise reaction time is 0.5~1 hour；It is cooled to 0~5 DEG C of heat preservation crystallization, the time is 0.5~1 hour；Through
Be filtered, washed 5- ethyl -5- (1- methyl butyl) barbiturates sodium wet product.
It is 29%~31% (w/w) that the methanol solution of the sodium methoxide, which is methanol sodium content,.
The drying process of the wet product of 5- ethyl -5- (1- methyl butyl) barbiturates sodium is to carry out under negative pressure, vacuum degree
≥-0.08MPa；40~60 DEG C of temperature, the time is 3~5 hours.
The present invention and the prior art have the advantages that the process stabilizing, easy to operate, with short production cycle, product quality
Good, purity is high, high income, production cost is low, and low energy consumption, and disposing mother liquor recycles, and the three wastes are few, is suitble to industrialized production.
Specific embodiment
Below with reference to embodiment, the present invention will be further described.
Embodiment 1:
Step A: 113.14g5- ethyl -5- (1- methyl butyl) malonyl urea is dissolved in 565.7g acetone, is crossed and is filtered out
Remove insoluble matter impurity.Filtrate is transferred in 2000ml reaction flask, under stirring, by filtered 97.8g methanol in 0.5 hour
The methanol solution of sodium (29%, w/w) is added drop-wise in reaction flask slowly, is continued to be stirred to react crystallization 0.5 hour, is cooled to 5 DEG C,
The wet product of 5- ethyl -5- (1- methyl butyl) barbiturates sodium is washed, is obtained in heat preservation crystallization 1 hour, filtering.
Step B: the step A wet product that 5- ethyl -5- (1- methyl butyl) barbiturates sodium is made is added to vacuum drying
In device, vacuum degree >=-0.08MPa is controlled, heat up drying, controls 40 DEG C of temperature, is dried in vacuo 5 hours, obtains 119.4g5- ethyl -
5- (1- methyl butyl) barbiturates sodium finished product, HPLC purity 99.87%, yield 96.19%.
Embodiment 2:
Step A: 113.14g5- ethyl -5- (1- methyl butyl) malonyl urea is dissolved in 1131g acetone, is crossed and is filtered out
Remove insoluble matter impurity.Filtrate is transferred in 2000ml reaction flask, under stirring, by filtered 95.8g sodium methoxide in 1 hour
The methanol solution of (31%, w/w) is added drop-wise in reaction flask slowly, continues to be stirred to react crystallization 1 hour, is cooled to 0 DEG C, heat preservation
The wet product of 5- ethyl -5- (1- methyl butyl) barbiturates sodium is washed, is obtained in crystallization 0.5 hour, filtering.
Step B: the step A wet product that 5- ethyl -5- (1- methyl butyl) barbiturates sodium is made is added to vacuum drying
In device, vacuum degree >=-0.08MPa is controlled, heat up drying, controls temperature 60 C, is dried in vacuo 3 hours, obtains 121.6kg5- second
Base -5- (1- methyl butyl) barbiturates sodium finished product, HPLC purity 99.80%, yield 97.96%.
Embodiment 3:
Step A: 113.14g5- ethyl -5- (1- methyl butyl) malonyl urea is dissolved in 848g acetone, is filtered to remove
Insoluble matter impurity.Filtrate is transferred in 2000ml reaction flask, under stirring, by filtered 97.2g sodium methoxide in 1 hour
The methanol solution of (30%, w/w) is added drop-wise in reaction flask slowly, continues to be stirred to react crystallization 0.5 hour, is cooled to 3 DEG C, is protected
The wet product of 5- ethyl -5- (1- methyl butyl) barbiturates sodium is washed, is obtained in temperature crystallization 1 hour, filtering.
Step B: the step A wet product that 5- ethyl -5- (1- methyl butyl) barbiturates sodium is made is added to vacuum drying
In device, vacuum degree >=-0.08MPa is controlled, heat up drying, controls temperature 50 C, is dried in vacuo 4 hours, obtains 120.9kg5- second
Base -5- (1- methyl butyl) barbiturates sodium finished product, HPLC purity 99.13%, yield 97.4%.
Claims (1)
1. a kind of preparation method of 5- ethyl -5- (1- methyl butyl) barbiturates sodium, it is characterised in that: this method includes two
Step:
A, 5- ethyl -5- (1- methyl butyl) malonyl urea acts on the methanol solution of sodium methoxide in acetone soln and 5- second is made
The wet product of base -5- (1- methyl butyl) barbiturates sodium；
The acetone soln of described 5- ethyl -5- (1- methyl butyl) malonyl urea, is according to 5- ethyl -5- (1- methyl butyl)
Malonyl urea and the mass ratio of solvent acetone 1:5~10 dissolve 5- ethyl -5- (1- methyl butyl) malonyl urea in acetone
It is made；
The methanol solution of the sodium methoxide is with weight ratio meter, and methanol sodium content is 29%~31%；
Molar ratio=1:1.05 of sodium methoxide in 5- ethyl -5- (1- methyl butyl) malonyl urea and methanol solution of sodium methylate~
1.1；
Under stirring at room temperature, methanolic sodium methoxide is added in the acetone soln of 5- ethyl -5- (1- methyl butyl) malonyl urea slowly
Crystallization of solution reaction, crystallization reaction time are 0.5~1 hour, are cooled to 0~5 DEG C of heat preservation crystallization, and the time is 0.5~1 hour,
Be filtered, washed 5- ethyl -5- (1- methyl butyl) barbiturates sodium wet product；
B, by the above-mentioned wet product for obtaining 5- ethyl -5- (1- methyl butyl) barbiturates sodium it is vacuum dried 5- ethyl -5- (1-
Methyl butyl) barbiturates sodium finished product；
The drying process of the wet product of described 5- ethyl -5- (1- methyl butyl) the barbiturates sodium is to carry out under negative pressure, vacuum
Degree >=-0.08MPa, 40~60 DEG C of temperature, the time is 3~5 hours.
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| CN201710386429.2A CN106986834B (en) | 2017-05-26 | 2017-05-26 | The preparation method of 5- ethyl -5- (1- methyl butyl) barbiturates sodium |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102435690A (en) * | 2011-11-24 | 2012-05-02 | 重庆警官职业学院 | Method for quickly detecting poison in liver |
-
2017
- 2017-05-26 CN CN201710386429.2A patent/CN106986834B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102435690A (en) * | 2011-11-24 | 2012-05-02 | 重庆警官职业学院 | Method for quickly detecting poison in liver |
Non-Patent Citations (2)
| Title |
|---|
| 戊巴比妥钠的合成工艺研究;刘子明，等;《化学试剂》;20111231;第33卷(第9期);857-858 * |
| 苯巴比妥的合成研究;韩建国，等;《安徽化工》;20070430;第33卷(第2期);42-43 * |
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