CN103130642A - Preparation method of 2-acetoxyl group methoxy group-1.3-propylene dichloride - Google Patents
Preparation method of 2-acetoxyl group methoxy group-1.3-propylene dichloride Download PDFInfo
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- CN103130642A CN103130642A CN 201110393596 CN201110393596A CN103130642A CN 103130642 A CN103130642 A CN 103130642A CN 201110393596 CN201110393596 CN 201110393596 CN 201110393596 A CN201110393596 A CN 201110393596A CN 103130642 A CN103130642 A CN 103130642A
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- propylene dichloride
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- acetoxyl group
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Abstract
Disclosed is a preparation method of 2-acetoxyl group methoxy group-1.3-propylene dichloride. The following substances are extracted according to weight ratio: 250kg of 1.3-dichloro-2-propyl alcohol, 60kg of paraformaldehyde, 3.68kg of vitriol, 250kg of acetic anhydride and 5kg of potassium acetate; the 1.3-dichloro-2-propyl alcohol, the paraformaldehyde and the vitriol are added to a clean and dry reaction still and are warmed slowly, the temperature rises to 96 DEG C to 98 DEG C in 2 hours, and heat preservation is carried out for 2 hours; the temperature is lowered to 10 DEG C after heat preservation, the acetic anhydride is dropped to the reaction still, and the temperature is kept between 15 DEG C and 20 DEG C; after the acetic anhydride is added, the temperature rises to 35 DEG C to 40 DEG C, and heat preservation is carried out for 10 hours; the potassium acetate is added to the reaction still, stirring is conducted, the acetic anhydride is recycled in vacuum to 100 DEG C, the temperature is lowered to 20 DEG C, and filtering is conducted; and filter liquor is pumped into a rectifying still, steamed cut fraction in a state of 115 DEG C/10mmHg is collected, and the 2-acetoxyl group methoxy group-1.3-propylene dichloride with 80% of weight yield and more than or equal to 95% of content is obtained. According to the preparation method of the 2-acetoxyl group methoxy group-1.3-propylene dichloride, production cost is reduced, and yield is improved.
Description
Technical field
The invention belongs to chemical industry field or pharmacy field, specifically refer to the preparation method of a kind of 2-acetoxyl group methoxyl group-1.3-propylene dichloride.
Background technology
2-acetoxyl group methoxyl group-1.3-propylene dichloride (hereinafter to be referred as the chlorine methoxyethoxy ester) is the main intermediate of antivirus raw material medicine ganciclovir, at home, all there is larger market the world.This product is continued to use initial process always from domestic putting goods on the market in 1998, be characterized in: 1, the production time long, about five days (120h); 2, production stage had 5 steps; 3, use a kind solvent purified petroleum benzin; 4, recovery rate only has 55% left and right.
Its chemical equation is:
The first step:
Second step:
Operation: add 1.3-two chloro-2 propyl alcohol that configure and stir in the 1000L of clean dried reactor, adding paraformaldehyde, finishing, slowly adding the vitriol oil, locking clean-out cover, slowly heating up, being warmed up to 96-98 ℃ in about 2 hours, and being incubated 2 hours.Insulation is finished, and cools to below 40 ℃, adds pure stupidly, is warming up to backflow, and reflux dewatering is to the greatest extent.Approximately need 16 hours, cool to below 30 ℃, add Potassium ethanoate 5kg, stirred rear standing 2 hours.
Extract supernatant liquor in still kettle, first normal pressure reclaims purified petroleum benzin to 100 ℃, cools to 60 ℃, and unreacted 1.3-two chloro-2 propyl alcohol of vacuum distilling cool to 60 ℃ to 140 ℃ of interior temperature, add ethanol 100kg, cool to 0 ℃ and get rid of material, get the acetal crude product.
Crude product adds 400kg ethanol rising temperature for dissolving, adds gac 5kg decolouring 30 minutes, filters, and filtrate is cooled to 0 ℃ and gets the acetal elaboration, and elaboration is in 40-50 ℃ of oven dry, weight yield 70%.
Get acetal 250kg aceticanhydride 375kg sulfuric acid 1.84kg Potassium ethanoate 2kg
Drop into aceticanhydride, acetal in the reactor of clean dried, slowly add sulfuric acid, in 80 ℃ of insulations 10 hours, cool to 30 ℃, add Potassium ethanoate to stir 15 minutes, steam diluted acid and be cooled to 10 ℃ of filtrations, in filtrate suction rectifying still, collect 115 ℃/10mmHg fraction, weight yield 75%, content 〉=90%.These all forms have certain limitation: or easily variable color or use inconvenience, or with high costs; Thereby be necessary to be innovated on this basis and explore new production technique.
Summary of the invention
The preparation method who the purpose of this invention is to provide a kind of 2-acetoxyl group methoxyl group-1.3-propylene dichloride.
Technical solution of the present invention is as follows:
The preparation method of a kind of 2-acetoxyl group methoxyl group-1.3-propylene dichloride is provided, and its chemical equation is as follows:
Only need sequentially choose reactant and resultant and one step of catalyzer completes following reaction:
It is characterized in that:
By weight extracting following material:
in the clean dried reactor, add 1.3-two chloro-2-propyl alcohol, paraformaldehyde, sulfuric acid, slowly heat up, be warming up to 96-98 ℃ in 2 hours, be incubated 2 hours, insulation is finished, cool to 10 ℃ and begin to drip aceticanhydride, temperature remains on 15-20 ℃, finish, heat up in 35-40 ℃ of insulation 10 hours, add Potassium ethanoate, stir, vacuum reclaims aceticanhydride to 100 ℃, be cooled to 20 ℃, filter, in filtrate suction rectifying still, collect the fraction that steams under 115 ℃/10mmHg state, namely get weight yield 80%, the 2-acetoxyl group methoxyl group of content 〉=95%-1.3-propylene dichloride.
The preparation method of 2-acetoxyl group methoxyl group as above-1.3-propylene dichloride, it is characterized in that: before described dropping aceticanhydride, steam under the 10mmHg state when adding 250kg rectifying less than 115 ℃ of fractions, the yield 90% of 2-acetoxyl group methoxyl group-1.3-propylene dichloride; This preparation method is applicable to since the second material.
Target:
1, do not use a kind solvent pure stupid.
2, reduce the aceticanhydride consumption, do not use ethanol, slightly increase the paraformaldehyde consumption.
3, time shorten to 50 hour.
4, cost only be equivalent to original half, quality has significantly and to improve, and can reach 99% (because the reaction times is short, side reaction is few, and impurity phase is conducive to fractionation to few).
Embodiment
The below provides embodiments of the invention, but is not limited to the present embodiment:
Embodiment 1:
By weight extracting following material:
In the clean dried reactor, add 1.3-two chloro-2-propyl alcohol, paraformaldehyde, sulfuric acid, slowly heat up, be warming up to 96-98 ℃ in 2 hours, be incubated 2 hours, insulation is finished, cool to 10 ℃ and begin to drip aceticanhydride, temperature remains on 15-20 ℃, finishes, heat up in 35-40 ℃ of insulation 10 hours, add Potassium ethanoate, stir, vacuum reclaims aceticanhydride to 100 ℃, be cooled to 20 ℃, filter, in filtrate suction rectifying still, collect 115 ℃/10mmHg fraction, namely get weight yield 80%, the 2-acetoxyl group methoxyl group of content 〉=95%-1.3-propylene dichloride.
Embodiment 2:
Since the second material, by weight extracting following material:
in the clean dried reactor, add 1.3-two chloro-2-propyl alcohol, paraformaldehyde, sulfuric acid, slowly heat up, be warming up to 96-98 ℃ in 2 hours, be incubated 2 hours, insulation is finished, cool to 10 ℃, when adding rectifying described in 250kg embodiment 1 at the 115 ℃/fraction that steams below 10mmHg, begin again to drip aceticanhydride, temperature remains on 15-20 ℃, finish, heat up in 35-40 ℃ of insulation 10 hours, add Potassium ethanoate, stir, vacuum reclaims aceticanhydride to 100 ℃, be cooled to 20 ℃, filter, in filtrate suction rectifying still, collect 115 ℃/10mmHg fraction, namely get weight yield 90%, the 2-acetoxyl group methoxyl group of content 〉=95%-1.3-propylene dichloride.
Although above shown detailed embodiment of the present invention, those skilled in the art is under prerequisite of the present invention, can carry out the part modifications and changes; The content of mentioning in description above is the illustration of property as an illustration only, is not limitation of the present invention, has the preparation method of the 2-acetoxyl group methoxyl group of technical characterictic of the present invention-1.3-propylene dichloride, all falls into scope of patent protection shown in the present.
Claims (2)
1. the preparation method of 2-acetoxyl group methoxyl group-1.3-propylene dichloride is characterized in that: by weight extracting following material:
in the clean dried reactor, add 1.3-two chloro-2-propyl alcohol, paraformaldehyde, sulfuric acid, slowly heat up, be warming up to 96-98 ℃ in 2 hours, be incubated 2 hours, insulation is finished, cool to 10 ℃ and begin to drip aceticanhydride, temperature remains on 15-20 ℃, finish, heat up in 35-40 ℃ of insulation 10 hours, add Potassium ethanoate, stir, vacuum reclaims aceticanhydride to 100 ℃, be cooled to 20 ℃, filter, in filtrate suction rectifying still, collect heating up in a steamer confusingly of steaming under 115 ℃/10mmHg state, namely get weight yield 80%, the 2-acetoxyl group methoxyl group of content 〉=95%-1.3-propylene dichloride.
2. the preparation method of 2-acetoxyl group methoxyl group as claimed in claim 1-1.3-propylene dichloride, it is characterized in that: before described dropping aceticanhydride, steam under/10mmHg state when adding 250kg rectifying less than the foreshot of 115 ℃, the yield 90% of 2-acetoxyl group methoxyl group-1.3-propylene dichloride.
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| CN 201110393596 CN103130642A (en) | 2011-11-30 | 2011-11-30 | Preparation method of 2-acetoxyl group methoxy group-1.3-propylene dichloride |
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| CN 201110393596 CN103130642A (en) | 2011-11-30 | 2011-11-30 | Preparation method of 2-acetoxyl group methoxy group-1.3-propylene dichloride |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103804192A (en) * | 2014-02-18 | 2014-05-21 | 安徽海康药业有限责任公司 | Method for preparing 1, 3-dihalogenated-2-propoxy methyl alcohol alkyl carboxylic ester |
| CN105837440A (en) * | 2016-04-13 | 2016-08-10 | 安徽海康药业有限责任公司 | Preparation technology of 1,3-dichloro-2-acetyl methoxy propane |
| CN107141291A (en) * | 2017-07-10 | 2017-09-08 | 湖北天义药业有限公司 | A kind of preparation method of GCV |
| CN113791149A (en) * | 2021-09-07 | 2021-12-14 | 石家庄四药有限公司 | Detection method of 1-chloro-3-methoxypropane related substances |
-
2011
- 2011-11-30 CN CN 201110393596 patent/CN103130642A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103804192A (en) * | 2014-02-18 | 2014-05-21 | 安徽海康药业有限责任公司 | Method for preparing 1, 3-dihalogenated-2-propoxy methyl alcohol alkyl carboxylic ester |
| CN103804192B (en) * | 2014-02-18 | 2015-12-02 | 安徽海康药业有限责任公司 | The preparation method of a kind of 1,3-dihalo-2-propoxy-methyl alcohol alkyl carboxylic acid ester |
| CN105837440A (en) * | 2016-04-13 | 2016-08-10 | 安徽海康药业有限责任公司 | Preparation technology of 1,3-dichloro-2-acetyl methoxy propane |
| CN105837440B (en) * | 2016-04-13 | 2018-12-11 | 安徽海康药业有限责任公司 | A kind of preparation process of the chloro- 2- acetyl group methoxy propane of 1,3- bis- |
| CN107141291A (en) * | 2017-07-10 | 2017-09-08 | 湖北天义药业有限公司 | A kind of preparation method of GCV |
| CN113791149A (en) * | 2021-09-07 | 2021-12-14 | 石家庄四药有限公司 | Detection method of 1-chloro-3-methoxypropane related substances |
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Application publication date: 20130605 |