CN101260100A - Preparation method for 5-hydroxymethylthiazole - Google Patents
Preparation method for 5-hydroxymethylthiazole Download PDFInfo
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- CN101260100A CN101260100A CNA2008100311147A CN200810031114A CN101260100A CN 101260100 A CN101260100 A CN 101260100A CN A2008100311147 A CNA2008100311147 A CN A2008100311147A CN 200810031114 A CN200810031114 A CN 200810031114A CN 101260100 A CN101260100 A CN 101260100A
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- ethyl acetate
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/24—Radicals substituted by oxygen atoms
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Abstract
The invention relates to a method for preparing 5-hydroxymethyl thiazole, which belongs to the drug production technical field. The invention includes the following steps that: the esterification between 2-chloro-5-chloromethyl thiazole and sodium acetate trihydrate is performed in ethanol; after purification, the product obtained from esterification is deoxidized in the ethanol by zinc powder; and then the product obtained from deoxidization is hydrolyzed by sodium hydroxide to obtain the target product, which is condensed, filtered and distilled to yield the final product. The method for preparing 5-hydroxymethyl thiazole provided by the invention is characterized in original technology, advanced technique, simplified technology, and safe production. The final product has the advantages of steady performance, high content and low impurities, etc.
Description
Technical field
The present invention relates to a kind of synthetic method of intermediate 5-hydroxymethylthiazole of hiv protease inhibitor, belong to technical field of pharmaceuticals.
Background technology
Ritonavir (ritonavir, trade(brand)name Norvir) is a kind of hiv protease inhibitor, has the activity of anti human immune deficiency virus (HIV), is developed by U.S. Ya Pei drugmaker.The 5-hydroxymethylthiazole is the key intermediate of synthetic ritonavir.
The synthetic method of the 5-hydroxymethylthiazole of domestic and foreign literature report has two kinds; a kind of is reaction with 2-halo mda compound and thioformamide; be lower than at moisture content under 5% the condition and obtain the 5-formyl thiazole; then with after the borane compound reduction; concentrate earlier; resistates adds water and alkali metal hydroxide arbitrarily, with the extraction agent extraction, removes solvent extraction 5-hydroxymethylthiazole by evaporation more then.
Another kind be with 2-chloro-5-5-chloromethyl thiazole and formate after reaction in the presence of a kind of quaternary amine phase-transfer catalyst, with the strong alkali aqueous solution reaction, obtain 2-chloro-5-hydroxymethylthiazole intermediate, in methyl alcohol, obtain product then through the high pressure shortening.
Above-mentioned two kinds of methods all exist operation dangerous, and raw and auxiliary material source is inconvenient, price is high, in the production process control loaded down with trivial details, shortcoming such as by product is more.
Summary of the invention
Technical problem to be solved by this invention is the deficiency that overcomes on the prior art, provides a kind of quality product height, aftertreatment is simple, cost is low, be beneficial to environmental protection, the preparation method of the 5-hydroxymethylthiazole of original creation advanced technologies route.
Summary of the invention
The technical solution used in the present invention is: 2-chloro-5-5-chloromethyl thiazole and sodium acetate trihydrate are carried out esterification in ethanol, behind the purifying, in ethanol, reduce esterification products with zinc powder, obtain target product with 10% sodium hydroxide hydrolysis again, through concentrate, filter, distillation obtains finished product;
Wherein, described 2-chloro-5-5-chloromethyl thiazole and sodium acetate trihydrate heat up 78 ℃ and carry out esterification in the presence of ethanol, after question response is finished, are cooled to room temperature, filter, and concentrate, and obtain intermediate 1 through ethyl acetate extraction, after concentrating; Described each raw materials in part by weight proportioning is as follows:
168 parts of 2-chloro-5-5-chloromethyl thiazoles
Dehydrated alcohol 480-600 part
Sodium acetate trihydrate 200-265 part
Ethyl acetate 150-260 part
The purge process of reacted reaction solution is included in the product that concentrates behind the ethanol and adds ethyl acetate, filters, concentrates and obtain intermediate 1;
After adding dehydrated alcohol, zinc powder, part Glacial acetic acid in the resulting intermediate 1, be heated to backflow, keep dripping remaining Glacial acetic acid, after question response is finished under the vigorous reflux state, the cooling room temperature, filter, reclaim ethanol, regulate pH=9-10 with ammoniacal liquor then, use ethyl acetate extraction, concentrate ethyl acetate then and obtain intermediate 2; Described each raw materials in part by weight proportioning is as follows:
Zinc powder 170-230 part
Glacial acetic acid 350-450 part
Ammoniacal liquor 500-600 part
Ethyl acetate 600-750 part
Add aqueous sodium hydroxide solution in the resulting intermediate 2, the 70 ℃ of hydrolysis that heat up after question response is finished, are used ethyl acetate extraction, concentrate, and obtain finished product through underpressure distillation.Described each raw materials in part by weight proportioning is as follows:
8-10% sodium hydroxide 400-500 part
Ethyl acetate 700-880 part
In the technique scheme, 2-chloro-5-5-chloromethyl thiazole and sodium acetate trihydrate heat up 78 ℃ in the presence of ethanol, keep slight boiling condition, until finishing reaction.
In the technique scheme, intermediate 1 adds zinc powder earlier in dehydrated alcohol, add the part Glacial acetic acid then, after reflux is brought out reaction, under vigorous reflux, drips remaining Glacial acetic acid again, finishes until reaction.
5-hydroxymethylthiazole preparation method of the present invention is the advanced technologies route of original creation, and is scientific and reasonable, operational safety, simple, and the chemical raw material convenient sources, with low cost, advantage such as products obtained therefrom content height, impurity are few.
The product that adopts preparation method of the present invention to make is carried out the quality approach test:
1, for test agent: our company's trial-production, lot number: 20071001,20071002,20071003
2, control sample: domestic certain factory's product, lot number 20070928A
3, experimental technique and project
Detect the every requirement down of (seeing appendix 1) 5-hydroxymethylthiazole item according to company standard, carry out complete and check trial-product (three batches) and reference substance are a collection of.
Every test-results is seen attached list:
Project outward appearance content (%) water content spectrogram
Control sample (20070928A) light yellow transparent liquid 98.7 0.38 is seen Fig. 1
20071001 light yellow transparent liquids 99.5 0.25 are seen Fig. 2
20071002 light yellow transparent liquids 99.3 0.30 are seen Fig. 3
20071003 light yellow transparent liquids 99.2 0.27 are seen Fig. 4
Conclusion: detect data and show that products made thereby quality of the present invention obviously is better than domestic like product.
Description of drawings:
Fig. 1 is the control sample content spectrogram of quality approach
Fig. 2 supplies test agent 20071001 content spectrograms for product of the present invention
Fig. 3 supplies test agent 20071002 content spectrograms for product of the present invention
Fig. 4 supplies test agent 20071003 content spectrograms for product of the present invention
Embodiment:
Embodiment 1
A kind of preparation method of 5-hydroxymethylthiazole, comprise 2-chloro-5-5-chloromethyl thiazole is reacted in ethanol with sodium acetate trihydrate earlier, use the zinc powder reduction esterification products then, obtain target product with sodium hydroxide hydrolysis again, obtain finished product through concentrating, filter, distilling.
Wherein, described 2-chloro-5-5-chloromethyl thiazole and sodium acetate trihydrate heat up 78 ℃ in the presence of ethanol, keep slight boiling condition, until finishing reaction.Described each raw materials in part by weight proportioning is as follows:
168 parts of 2-chloro-5-5-chloromethyl thiazoles
480 parts of dehydrated alcohols
200 parts of sodium acetate trihydrates
150 parts of ethyl acetate
The reduction reaction of described zinc powder in ethanol refers to intermediate 1 in dehydrated alcohol, adds zinc powder earlier, adds the part Glacial acetic acid then, after reflux is brought out reaction, under vigorous reflux, drips remaining Glacial acetic acid again, keeps 79 ℃ then, finishes until reaction.Be cooled to 25 ℃ then, filter, reclaim ethanol.Regulate pH=9-10 with ammoniacal liquor, add ethyl acetate extraction, concentrated solvent obtains intermediate 2.Described each raw materials in part by weight proportioning is as follows:
170 parts of zinc powders
350 parts in Glacial acetic acid
500 parts of ammoniacal liquor
600 parts of ethyl acetate
Described intermediate 2 hydrolysis reaction in aqueous sodium hydroxide solution refers in intermediate 2 to add the sodium hydroxide solution of 8%-10%, and 70 ℃ of hydrolysis 3 hours are cooled to 25 ℃, add ethyl acetate extraction then, concentrate, and obtain finished product through underpressure distillation.Described each raw materials in part by weight proportioning is as follows:
400 parts in 8-10% sodium hydroxide
700 parts of ethyl acetate
Detailed process is:
In dehydrated alcohol, stir adding sodium acetate trihydrate down.The heating for dissolving sodium acetate trihydrate adds 12-chloro-5-5-chloromethyl thiazole then, and 78 ℃, until finishing reaction.After being cooled to room temperature, filter, use the absolute ethanol washing filter residue, merging filtrate behind the recovery ethanol, adds ethyl acetate, stirring and dissolving, and cooling is filtered, and washs filter residue with ethyl acetate, and merging filtrate reclaims ethyl acetate.Obtain intermediate 1.
Intermediate 1 is dissolved in dehydrated alcohol and the acetic acid, stirs adding zinc powder down, be heated to the backflow induced reaction and take place, drip acetic acid then and keep vigorous reflux, after adding, reflux is finished until reaction.Be cooled to 25 ℃, filter.Solid filter residue dehydrated alcohol thorough washing behind the filtrate recycling ethanol, is regulated pH=9-10 with ammoniacal liquor, adds ethyl acetate extraction, layering, and organic phase reclaims ethyl acetate and obtains intermediate 2.
Intermediate 2 is dissolved in 10% sodium hydroxide, at 70 ℃ of constant temperature hydrolysis 3h, is cooled to 25 ℃, add the ethyl acetate extraction layering, organic phase reclaims ethyl acetate, obtains thick product.106-112 ℃ of cut collected in 3000Pa (0.003MPa or 22mmHg) underpressure distillation, obtains qualified product.
Embodiment 2
A kind of preparation method of 5-hydroxymethylthiazole, comprise 2-chloro-5-5-chloromethyl thiazole is reacted in ethanol with sodium acetate trihydrate earlier, use the zinc powder reduction esterification products then, obtain target product with sodium hydroxide hydrolysis again, obtain finished product through concentrating, filter, distilling.
Wherein, described 2-chloro-5-5-chloromethyl thiazole and sodium acetate trihydrate heat up 78 ℃ in the presence of ethanol, keep slight boiling condition, until finishing reaction.Described each raw materials in part by weight proportioning is as follows:
168 parts of 2-chloro-5-5-chloromethyl thiazoles
550 parts of dehydrated alcohols
230 parts of sodium acetate trihydrates
235 parts of ethyl acetate
The reduction reaction of described zinc powder in ethanol refers to intermediate 1 in dehydrated alcohol, adds zinc powder earlier, adds the part Glacial acetic acid then, after reflux is brought out reaction, under vigorous reflux, drips remaining Glacial acetic acid again, keeps 79 ℃ then, finishes until reaction.Be cooled to 25 ℃ then, filter, reclaim ethanol.Regulate pH=9-10 with ammoniacal liquor, add ethyl acetate extraction, concentrated solvent obtains intermediate 2.Described each raw materials in part by weight proportioning is as follows:
220 parts of zinc powders
420 parts in Glacial acetic acid
560 parts of ammoniacal liquor
680 parts of ethyl acetate
Described intermediate 2 hydrolysis reaction in aqueous sodium hydroxide solution refers in intermediate 2 to add the sodium hydroxide solution of 8%-10%, and 70 ℃ of hydrolysis 3 hours are cooled to 25 ℃, add ethyl acetate extraction then, concentrate, and obtain finished product through underpressure distillation.Described each raw materials in part by weight proportioning is as follows:
480 parts in 8-10% sodium hydroxide
800 parts of ethyl acetate
Detailed process is:
In dehydrated alcohol, stir adding sodium acetate trihydrate down.The heating for dissolving sodium acetate trihydrate adds 12-chloro-5-5-chloromethyl thiazole then, and 78 ℃, until finishing reaction.After being cooled to room temperature, filter, use the absolute ethanol washing filter residue, merging filtrate behind the recovery ethanol, adds ethyl acetate, stirring and dissolving, and cooling is filtered, and washs filter residue with ethyl acetate, and merging filtrate reclaims ethyl acetate.Obtain intermediate 1.
Intermediate 1 is dissolved in dehydrated alcohol and the acetic acid, stirs adding zinc powder down, be heated to the backflow induced reaction and take place, drip acetic acid then and keep vigorous reflux, after adding, reflux is finished until reaction.Be cooled to 25 ℃, filter.Solid filter residue dehydrated alcohol thorough washing behind the filtrate recycling ethanol, is regulated pH=9-10 with ammoniacal liquor, adds ethyl acetate extraction, layering, and organic phase reclaims ethyl acetate and obtains intermediate 2.
Intermediate 2 is dissolved in 10% sodium hydroxide, at 70 ℃ of constant temperature hydrolysis 3h, is cooled to 25 ℃, add the ethyl acetate extraction layering, organic phase reclaims ethyl acetate, obtains thick product.106-112 ℃ of cut collected in 3000Pa (0.003MPa or 22mmHg) underpressure distillation, obtains qualified product.
Embodiment 3
A kind of preparation method of 5-hydroxymethylthiazole, comprise 2-chloro-5-5-chloromethyl thiazole is reacted in ethanol with sodium acetate trihydrate earlier, use the zinc powder reduction esterification products then, obtain target product with sodium hydroxide hydrolysis again, obtain finished product through concentrating, filter, distilling.
Wherein, described 2-chloro-5-5-chloromethyl thiazole and sodium acetate trihydrate heat up 78 ℃ in the presence of ethanol, keep slight boiling condition, until finishing reaction.Described each raw materials in part by weight proportioning is as follows:
168 parts of 2-chloro-5-5-chloromethyl thiazoles
580 parts of dehydrated alcohols
245 parts of sodium acetate trihydrates
240 parts of ethyl acetate
The reduction reaction of described zinc powder in ethanol refers to intermediate 1 in dehydrated alcohol, adds zinc powder earlier, adds the part Glacial acetic acid then, after reflux is brought out reaction, under vigorous reflux, drips remaining Glacial acetic acid again, keeps 79 ℃ then, finishes until reaction.Be cooled to 25 ℃ then, filter, reclaim ethanol.Regulate pH=9-10 with ammoniacal liquor, add ethyl acetate extraction, concentrated solvent obtains intermediate 2.Described each raw materials in part by weight proportioning is as follows:
225 parts of zinc powders
435 parts in Glacial acetic acid
580 parts of ammoniacal liquor
720 parts of ethyl acetate
Described intermediate 2 hydrolysis reaction in aqueous sodium hydroxide solution refers in intermediate 2 to add the sodium hydroxide solution of 8%-10%, and 70 ℃ of hydrolysis 3 hours are cooled to 25 ℃, add ethyl acetate extraction then, concentrate, and obtain finished product through underpressure distillation.Described each raw materials in part by weight proportioning is as follows:
500 parts in 8-10% sodium hydroxide
850 parts of ethyl acetate
Detailed process is:
In dehydrated alcohol, stir adding sodium acetate trihydrate down.The heating for dissolving sodium acetate trihydrate adds 12-chloro-5-5-chloromethyl thiazole then, and 78 ℃, until finishing reaction.After being cooled to room temperature, filter, use the absolute ethanol washing filter residue, merging filtrate behind the recovery ethanol, adds ethyl acetate, stirring and dissolving, and cooling is filtered, and washs filter residue with ethyl acetate, and merging filtrate reclaims ethyl acetate.Obtain intermediate 1.
Intermediate 1 is dissolved in dehydrated alcohol and the acetic acid, stirs adding zinc powder down, be heated to the backflow induced reaction and take place, drip acetic acid then and keep vigorous reflux, after adding, reflux is finished until reaction.Be cooled to 25 ℃, filter.Solid filter residue dehydrated alcohol thorough washing behind the filtrate recycling ethanol, is regulated pH=9-10 with ammoniacal liquor, adds ethyl acetate extraction, layering, and organic phase reclaims ethyl acetate and obtains intermediate 2.
Intermediate 2 is dissolved in 10% sodium hydroxide, at 70 ℃ of constant temperature hydrolysis 3h, is cooled to 25 ℃, add the ethyl acetate extraction layering, organic phase reclaims ethyl acetate, obtains thick product.106-112 ℃ of cut collected in 3000Pa (0.003MPa or 22mmHg) underpressure distillation, obtains qualified product.
Described 2-chloro-5-5-chloromethyl thiazole outward appearance is light yellow transparent liquid, and up to specification during discriminating, content 〉=98.0%, fusing point are 29-30 ℃, and boiling point is 108-110 ℃/18mmHg.
Described ethanol outward appearance is colourless transparent liquid, content 〉=99.7% moisture content≤0.3%
Described ethyl acetate outward appearance is colourless transparent liquid, content 〉=99.5%
Described ammoniacal liquor outward appearance is colourless transparent liquid, content 〉=27.0%
Described sodium acetate trihydrate appearance white transparent solid, content 〉=99.0%
Described zinc powder outward appearance gray solid, content 〉=99.0%
Appendix 1:
5-hydroxymethylthiazole company standard
1. purpose
1.1 for the accuracy that guarantees inspection after construction with have trackability, be convenient to selective examination, check, satisfy the supervision and management requirement, distinguish quality responsibility, specially formulate this inspection procedure.
2. responsibility
2.1 Quality Control Department of company is responsible for establishment, revision and the explanation of this system.
3. scope
3.1 this standard code the technical requirements of this product, test method, inspection rule, sign, packing, transportation, storage.
This standard adaptation is in the 5-hydroxymethylthiazole, and it is synthetic that this raw material is used for the AIDS resisting medicine intermediate.
4. structural formula and molecular formula
C
4H
5NOS 115.15
5. reference to standard
HNPZ07-05 " chemical examination is sampled, management system keeps sample ";
Two appendix VIII of Pharmacopoeia of the People's Republic of China version in 2005 M aquametry;
6. quality standard
The index name index
The outward appearance light yellow viscous liquid
Content (%) 〉=98.5
Moisture content (%)≤0.5%
7. test method
7.1 outward appearance:
Eyesight detects.
7.2 content:
7.2.1 detection method: GC method
7.2.2 testing conditions: adopt the general low-pole column of 30m, temperature programming detects.Heating schedule is: 60 degree sample introductions, keep 2min, and with 10 degree/min, be warmed up to 100 degree, keep 5min, with 3 degree/min, be warmed up to 145 degree, with 5 degree/min, be warmed up to 200 degree, keep 8min.Fid detector, 280 degree.Sample introduction temperature 200 degree.
7.3 moisture content:
Precision is measured trial-product 0.20g, measures by two appendix VIII of Pharmacopoeia of the People's Republic of China version in 2005 M aquametry.
8 inspection rules
8.1 this standard adopts pattern check and routine inspection.
Product should carry out type approval test when one of following situation:
A) after formal production identified in trial production of new products, as material, structure, technology bigger change is arranged, in the time that product performance may being influenced;
B) product stops production for a long time, when resuming production;
When c) factory inspection result and type approval test last time have than big-difference;
When d) national quality supervisory organ proposes the pattern survey requirement;
E) every two years carry out once during continuous production.
Type approval test project: be whole projects of this standard code.
Sampling: from the qualified product of factory inspection, produce representational sample at random and test, or carry out by the regulation of check detailed rules and regulations.
Outward appearance, content, moisture content adopt routine inspection, answer lot-by-lot inspection.Differentiate and test on demand.
8.2 group is criticized: behind the batch mixing, can mix by rectification under vacuum in producing and criticize in the production.
8.3 sampling method: according to HNPZ07-05 " chemical examination is sampled, management system keeps sample ".
8.4 judge: if defective item is arranged, can from this batch product, double sampling again and recheck in the check, and rechecking the result as last judgment basis, or by the regulation execution of check detailed rules and regulations.
9 signs, packing, transportation, storage
9.1 sign
The packing mark of product must meet No. 172 (1997) " identification of product mark regulations " of State Bureau of Technical Supervision, and following content is arranged:
A) maker's name and address;
B) date manufactured;
C) name of product;
D) lot identification mark and net weight.
9.2 packing
The 5-hydroxymethylthiazole adopts plastic tank; The lined with polyethylene bag film; Packaging vessel should be able to be airtight, and shading helps guaranteeing the quality and the convenient transportation of product and storing.The packing of product is a net weight 25KG/ bucket.
9.3 transportation and storage
Should avoid Exposure to Sunlight in the Product transport.
Product is stored in cool place, ventilation,
Storage temperature is below 25 ℃.
9.4 product is responsible for the phase
Product is responsible for phase from the date manufactured and is started at, and is meeting packing, transportation
Claims (4)
1, a kind of preparation method of 5-hydroxymethylthiazole, it is characterized in that 2-chloro-5-5-chloromethyl thiazole and sodium acetate trihydrate are reacted in ethanol, behind the purifying, use the zinc powder reduction esterification products, obtain target product with 10% sodium hydroxide hydrolysis again, obtain finished product through concentrating, filter, distilling;
Wherein, described 2-chloro-5-5-chloromethyl thiazole and sodium acetate trihydrate heat up 78 ℃ and carry out esterification in the presence of ethanol, after question response is finished, are cooled to room temperature, filter, and concentrate, and obtain intermediate 1 through ethyl acetate extraction, after concentrating; Described each raw materials in part by weight proportioning is as follows:
168 parts of 2-chloro-5-5-chloromethyl thiazoles
Dehydrated alcohol 480-600 part
Sodium acetate trihydrate 200-265 part
Ethyl acetate 150-260 part
The purge process of reacted reaction solution is included in the product that concentrates behind the ethanol and adds ethyl acetate, filters, concentrates and obtain intermediate 1;
After adding dehydrated alcohol, zinc powder, part Glacial acetic acid in the resulting intermediate 1, be heated to backflow, keep dripping remaining Glacial acetic acid, after question response is finished under the vigorous reflux state, the cooling room temperature, filter, reclaim ethanol, regulate pH=9-10 with ammoniacal liquor then, use ethyl acetate extraction, concentrate ethyl acetate then and obtain intermediate 2; Described each raw materials in part by weight proportioning is as follows:
Zinc powder 170-230 part
Glacial acetic acid 350-450 part
Ammoniacal liquor 500-600 part
Ethyl acetate 600-750 part
Add aqueous sodium hydroxide solution in the resulting intermediate 2, the 70 ℃ of hydrolysis that heat up after question response is finished, are used ethyl acetate extraction, concentrate, and obtain finished product through underpressure distillation.Described each raw materials in part by weight proportioning is as follows:
8-10% sodium hydroxide 400-500 part
Ethyl acetate 700-880 part
2, the preparation method of 5-hydroxymethylthiazole according to claim 1 is characterized in that 2-chloro-5-5-chloromethyl thiazole and sodium acetate trihydrate in the presence of ethanol, heats up 78 ℃, keeps slight boiling condition, until finishing reaction.
3, the preparation method of 5-hydroxymethylthiazole as claimed in claim 1 is characterized in that intermediate 1 in dehydrated alcohol, adds zinc powder earlier, add the part Glacial acetic acid then, after reflux is brought out reaction, under vigorous reflux, drip remaining Glacial acetic acid again, finish until reaction.
4, the preparation method of 5-hydroxymethylthiazole as claimed in claim 1 adds the sodium hydroxide solution of 8%-10%, 70 ℃ of hydrolysis 3 hours.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008100311147A CN101260100A (en) | 2008-04-21 | 2008-04-21 | Preparation method for 5-hydroxymethylthiazole |
| PCT/CN2008/001018 WO2009129661A1 (en) | 2008-04-21 | 2008-05-26 | A process for preparing 5-hydroxymethylthiazole |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008100311147A CN101260100A (en) | 2008-04-21 | 2008-04-21 | Preparation method for 5-hydroxymethylthiazole |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101260100A true CN101260100A (en) | 2008-09-10 |
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ID=39960832
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2008100311147A Pending CN101260100A (en) | 2008-04-21 | 2008-04-21 | Preparation method for 5-hydroxymethylthiazole |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN101260100A (en) |
| WO (1) | WO2009129661A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101863853B (en) * | 2009-12-28 | 2012-12-19 | 安徽贝克联合制药有限公司 | Technique for preparing 5-hydroxymethyl thiazole by one pot method |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116375662A (en) * | 2022-12-30 | 2023-07-04 | 新沂市砥研医药技术研究院有限公司 | Efficient purification process of 5-hydroxymethyl thiazole pharmaceutical intermediate |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE69520368T2 (en) * | 1994-11-22 | 2001-06-28 | Abbott Lab | METHOD FOR PRODUCING 5-HYDROXYMETHYL THIAZOLE |
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2008
- 2008-04-21 CN CNA2008100311147A patent/CN101260100A/en active Pending
- 2008-05-26 WO PCT/CN2008/001018 patent/WO2009129661A1/en active Application Filing
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101863853B (en) * | 2009-12-28 | 2012-12-19 | 安徽贝克联合制药有限公司 | Technique for preparing 5-hydroxymethyl thiazole by one pot method |
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| WO2009129661A1 (en) | 2009-10-29 |
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