GB2324089A - Process for the production of a thiazolidine derivative - Google Patents
Process for the production of a thiazolidine derivative Download PDFInfo
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- GB2324089A GB2324089A GB9807505A GB9807505A GB2324089A GB 2324089 A GB2324089 A GB 2324089A GB 9807505 A GB9807505 A GB 9807505A GB 9807505 A GB9807505 A GB 9807505A GB 2324089 A GB2324089 A GB 2324089A
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- dione
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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
- C07D277/32—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/34—Oxygen atoms
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Abstract
The phenolic hydroxyl group of 5-(4-hydroxybenzyl)thiazolidine-2,4-dione is protected with an acyl group; the resulting material is subjected to triphenylmethylation with triphenylmethyl chloride and then deacylated; thereby, intended 5-(4-hydroxybenzyl)-3-triphenylmethylthiazolidine-2,4-dione can be produced at a high yield.
Description
The present invention relates to a process for producing 5-(4-hydroxybenzyl)-3-triphenylmethylthiazolidine-2,4-dione. The compound obtained by the present invention is useful as a raw material for medicines, agricultural chemicals, etc.
For production of 5-(4-hydroxybenzyl)-3triphenylmethylthiazolidine-2,4-dione, a process described in JP-A-5-239041 is known. In this process, however, the 5-(4-acetoxybenzylidene)thiazolidine-2,4 dione formed as an intermediate has a very low solubility in organic solvent and the reduction reaction does not proceed effectively in an organic solvent; therefore, a severe condition of heating in an acetic acid solvent has had to be employed. This severe condition may give rise to side reactions (e.g. cleavage of thiazolidine ring) in the reduction reaction and has been an obstacle to the isolation and purification of intended product. The acetic acid used as a solvent is inconvenient in the subsequent acylation step and triphenylmethylation step and is preferably removed completely; thus, much labor and time have been required for complete removal. Further, in the triphenylmethylation step, since triethylamine is used in an equimolar amount to the substrate, the yield has been as low as 50% or less; and the presence of triphenylmethyl chloride, triphenylmethyl alcohol (derived from triphenylmethyl chloride) and 5-(4-acetoxybenzyl)thiazolidine-2,4-dione (an unreacted intermediate) has made complicated the purification of intended product.
Furthermore, in the final deacylation step, the operation is complicated, that is, the reaction is conducted in a toluene solvent and extraction with ethyl acetate is conducted in the post-treatment; moreover, use of three kinds of solvents has made their recovery difficult and has been uneconomical.
The present inventors made a study in order to solve the above-mentioned problems of the prior art. As a result, the present inventors have found out that by using, as a starting substance, 5-(4-hydroxybenzyl)thiazolidine-2,4-dione of high solubility, 5-(4hydroxybenzyl)-3-triphenylmethylthiazolidine-2,4-dione can be produced via a 5-(4-acyloxybenzyl)thiazolidine2,4-dione, at a high yield. The finding has led to the completion of the present invention.
The object of the present invention is to produce 5- ( 4-hydroxybenzyl ) -3-triphenylmethylthia- zolidine-2,4-dione at a high yield.
The present invention lies in a process for producing 5-(4-hydroxybenzyl)-3-triphenylmethylthiazolidine-2,4-dione via a 5-(4-acyloxybenzyl)thiazolidine-2,4-dione, which process comprises:
(a) a first step of protecting the phenolic hydroxyl group of 5-(4-hydroxybenzyl)thiazolidine-2,4 dione with an acyl group,
(b) a second step of reacting the 5-(4acyloxybenzyl)thiazolidine-2,4-dione represented by the following general formula (1) obtained in the above first step, with triphenylmethyl chloride:
(wherein Rl is an alkyl group having 1-3 carbon atoms or a phenyl group), and
(c) a third step of removing the acyl group of the 5- ( 4-acyloxybenzyl )-3-triphenylmethylthiazolidine- 2,4-dione represented by the following general formula (2) obtained in the above second step:
(wherein R1 has the same definition as given above).
The present invention is hereinafter described in detail.
The 5-( 4-hydroxybenzyl )thiazolidine-2 ,4-dione used as a starting material in the present invention is produced by the following process.
4-Hydroxybenzaldehyde is reacted with thiazolidine-2,4-dione in the presence of a small amount of piperidine, acetic acid or the like in an organic solvent (e.g. toluene) to obtain 5-(4-hydroxybenzylidene)thiazolidine-2,4-dione. Then, reduction is conducted in the presence of a catalyst in a solvent (e.g. methanol) under hydrogen pressure according to the process described in Japanese Patent Application No.
103220/1995 to obtain 5-(4-hydroxybenzyl)thiazolidine2,4-dione of low acetic acid content.
The first step of the present invention is a step of protecting the phenolic hydroxyl group of the 5 (4-hydroxybenzyl)thiazolidine-2,4-dione obtained as above, with an acyl group. The reaction is preferably conducted in the presence of a base in an organic solvent.
As the acylating agent used in the first step, there can be mentioned acid anhydrides such as acetic anhydride, propionic anhydride and the like; and acid chlorides such as acetyl chloride, propionyl chloride, butanoyl chloride, benzoyl chloride and the like. The amount of the acylating agent used is 1-2 equivalents, preferably 1-1.2 equivalents relative to 5-(4-hydroxybenzyl)thiazolidine-2,4-dione.
As the base used in the first step, there can be mentioned pyridine and tertiary amines represented by the following general formula (3):
(wherein R2, R3 and R4 may be the same or different and are each an alkyl group of 1-3 carbon atoms or a phenyl group, and R3 and R4may form a ring together).
Specific examples of the base are trialkylamines such as trimethylamine, triethylamine and the like; cyclic amines such as N-methylmorpholine, Nmethylpiperidine and the like; N,N-dimethylaniline; and pyridine. The amount of the base used may be equimolar or in excess to the acylating agent.
The solvent used in the reaction of the first step can be a single or mixed organic solvent inert to the reaction. Examples of the solvent are aromatic hydrocarbons such as toluene, xylene and the like; halogenated hydrocarbons such as dichloromethane, chloroform and the like; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, 1,4-dioxane and the like; esters such as ethyl acetate, methyl acetate and the like; and nitriles such as acetonitrile and the like. Preferable solvents are ethyl acetate, methyl acetate and acetonitrile.
The reaction temperature used in the first step is 0-1000C, preferably 10-40"C. The reaction time differs depending upon the base or reaction temperature used, but is usually within 12 hours, preferably 0.5-6 hours.
The second step of the present invention is a triphenylmethylation step of reacting the 5-(4acyloxybenzyl)thiazolidine-2,4-dione represented by the following general formula (1) obtained in the above first step, with triphenylmethyl chloride. As in the first step, the reaction is preferably conducted in the presence of a base in an organic solvent.
(wherein R1 is an alkyl group having 1-3 carbon atoms or a phenyl group).
The sufficient amount of triphenylmethyl chloride used in the second step is equimolar to the 5 (4-acyloxybenzyl)thiazolidine-2,4-dione to be reacted with triphenylmethyl chloride. Use of triphenylmethyl chloride in an excessive amount of 1.5 equivalents or more is not preferable because triphenyl alcohol difficult to remove is formed.
The base used in the second step is the same as used in the first step, i.e. pyridine or a tertiary amine represented by the following general formula (3):
(wherein R2, R3 and R4 may be the same or different and are each an alkyl group of 1-3 carbon atoms or a phenyl group, and R3 and R4may form a ring together).
Specific examples of the base are trialkylamines such as trimethylamine, triethylamine and the like; cyclic amines such as N-methylmorpholine, Nmethylpiperidine and the like; N,N-dimethylaniline; and pyridine. The amount of the base used is 1.5 equivalents or more, preferably 2-3 equivalents relative to the 5-(4-acyloxybenzyl)thiazolidine-2,4-dione to be reacted with triphenylmethyl chloride.
The solvent used in the reaction of the second step can be a single or mixed organic solvent inert to the reaction. Examples of the solvent are aromatic hydrocarbons such as toluene, xylene and the like; halogenated hydrocarbons such as dichloromethane, chloroform and the like; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, 1,4-dioxane and the like; esters such as ethyl acetate, methyl acetate and the like; and nitriles such as acetonitrile and the like. Preferable solvents are ethyl acetate, methyl acetate and acetonitrile.
The reaction temperature used in the second step is 0-100 C, preferably 10-40"C. The reaction time differs depending upon the base or reaction temperature used, but is usually within 12 hours, preferably 0.5-6 hours.
The first step and the second step can be conducted in the same reactor by using a common solvent.
That is, the reaction product of the first step can be used in the second step without being subjected to an isolation operation.
The third step of the present invention is a step of removing the acyl group (used as a protective group) of the 5-(4-acyloxybenzyl)-3-triphenylmethylthiazolidine-2,4-dione represented by the following general formula (2) obtained in the above second step:
(wherein R1 is an alkyl group having 1 to 3 carbon atoms or a phenyl group).
The deacylation reaction of the third step is preferably conducted in the presence of a sodium alkoxide in an alcohol solvent.
As the sodium alkoxide used in the third step, there can be mentioned sodium methoxide, sodium ethoxide, sodium isopropoxide, etc. with sodium methoxide being preferred for an economical reason. The amount of the sodium alkoxide used may be equimolar or in excess to the N-(triphenylmethyl)acyloxybenzylthiazolidine derivative to be deacylated.
The solvent used in the reaction of the third step is an alcohol corresponding to the sodium alkoxide, such as methanol, ethanol, isopropanol or the like.
The reaction temperature used in the third step is 0-100 C, preferably 10-40"C. The reaction time differs depending upon the base or reaction temperature used, but is usually within 12 hours, preferably 0.5-6 hours.
Next, the present invention is described specifically by way of Examples. However, the present invention is in no means restricted to these Examples.
Reference Example 1
Production of 5-(4-hydroxybenzylidene)thiazolidine 2, 4-dione There were mixed 122.2 g of 4-hydroxybenzaldehyde, 17.2 g of thiazolidine-2,4-dione, 8.5 g of piperidine, 6.0 g of acetic acid and 2,000 ml of toluene. The mixture was ref fluxed for 2 hours with heating. The reaction mixture was cooled to room temperature. The resulting crystals were collected by filtration, then washed with 500 ml of methanol and 400 ml of water, and vacuum-dried to obtain 198.8 g (yield: 90.0%) of a title compound as yellow crystals.
Reference Example 2
Production of 5- ( 4-hydroxybenzyl ) thiazolidine-2, 4-dione Into a pressure reactor were fed 100 g of 5 (4-hydroxybenzylidene)thiazolidine-2,4-dione and 1,250 ml of methanol. Thereto was added 10.0 g of a Raney nickel catalyst. The gas inside the reactor was replaced by hydrogen. The reactor contents were stirred at a hydrogen pressure of 10 kg/cm2 at 300C for 5 hours.
The reaction mixture was filtered to remove the catalyst. The filtrate was concentrated under reduced pressure to obtain 99.5 g (yield: 98.6%) of a colorless title compound.
Example 1 (1) Production of 5-(4-acetoxybenzyl)thiazolidine 2, 4-dione To 600 ml of toluene were added 44.6 g of 5 (4-hydroxybenzyl)thiazolidine-2,4-dione, 15.8 g of pyridine and 20.4 g of acetic anhydride. The mixture was stirred at 250C for 3 hours. The reaction mixture was washed with 600 ml of water. The organic layer was dried on anhydrous magnesium sulfate. The desiccant was removed by filtration. The filtrate was concentrated to obtain 50.8 g (yield: 95.8%) of a title compound as colorless crystals.
(2) Production of 5-(4-acetoxybenzyl)-3-triphenyl
methylthiazolidine-2,4-dione
To 200 ml of dichloromethane were added 50 g of the 5- (4-acetoxybenzyl )thiazolidine-2 , 4-dione obtained in above (1), 52.8 g of triethylamine and 52.8 g of triphenylmethyl chloride. The mixture was stirred at 25"C for 3 hours. The reaction mixture was washed with 200 ml of water. The organic layer was dried on anhydrous magnesium sulfate. The desiccant was removed by filtration. The filtrate was concentrated. The concentrate was washed with 200 ml of methanol to obtain 87.3 g (yield: 91.1%) of a title compound as colorless crystals.
(3) Production of 5-(4-hydroxybenzyl)-3-triphenyl
methylthiazolidine-2,4-dione
8.4 g of 28% sodium methoxide was dropwise added to a suspension of 20 g of the 5-(4-acetoxybenzyl)-3-triphenylmethylthiazolidine-2,4-dione obtained in above (2), in 200 ml of methanol. The mixture was stirred at 250C for 3 hours. To the reaction mixture was added 200 ml of water, followed by neutralization with dilute hydrochloric acid. The resulting crystals were collected by filtration and dried to obtain 15.6 g (yield: 85.0%) of a title compound as colorless crystals.
The overall yield of (1) to (3) was 74.2%.
Example 2 (1) Production of 5-(4-acetoxybenzyl)-3-triphenyl
methylthiazolidine-2,4-dione
To 300 ml of dichloromethane were added 22.3 g of 5-(4-hydroxybenzyl)thiazolidine-2,4-dionet 10.1 g of triethylamine and 10.2 g of acetic anhydride. The mixture was stirred at 250C for 3 hours. Thereto were added 27.9 g of triethylamine and 27.9 g of triphenylmethyl chloride, followed by stirring for 3 hours. The reaction mixture was washed with 300 ml of water. The organic layer was dried on anhydrous magnesium sulfate.
The desiccant was removed by filtration. The filtrate was concentrated. The concentrate was washed with 400 ml of methanol to obtain 43.0 g (yield: 84.8%) of a title compound as colorless crystals.
(2) Production of 5-(4-hydroxybenzyl)-3-triphenyl
methylthiazolidine-2,4-dione
This step was conducted in the same manner as in (3) of Example 1.
The overall yield of (1) to (2) was 72.1%.
Example 3 (1) Production of 5-(4-acetoxybenzyl)-3-triphenyl
methylthiazolidine-2,4-dione
To 400 ml of ethyl acetate were added 22.3 g of 5-(4-hydroxybenzyl)thiazolidine-2,4-dione, 10.1 g of triethylamine and 10.2 g of acetic anhydride. The mixture was stirred at 600C for 4 hours. The reaction mixture was washed with 40 ml of water. The organic layer was dried on anhydrous magnesium sulfate. The desiccant was removed by filtration. To the filtrate were added 27.9 g of triethylamine and 27.9 g of triphenylmethyl chloride, followed by stirring at 60"C for 2 hours. The reaction mixture was concentrated. To the concentrate was added 200 ml of methanol. The resulting crystals were collected by filtration to obtain 41.0 g (yield: 80.9%) of a title compound as colorless crystals.
(2) Production of 5-(4-hydroxybenzyl)-3-triphenyl
methylthiazolidine-2,4-dione
This step was conducted in the same manner as in (3) of Example 1.
The overall yield of (1) to (2) was 68.8%.
Example 4 (1) Production of 5-(4-acetoxybenzyl)-3-triphenyl
methylthiazolidine-2,4-dione
To 300 ml of acetonitrile were added 22.3 g of 5-(4-hydroxybenzyl)thiazolidine-2,4-dione, 10.1 g of triethylamine and 10.2 g of acetic anhydride. The mixture was stirred at 600C for 3 hours. The reaction mixture was concentrated under reduced pressure. The concentrate was poured into 200 ml of water. The resulting crystals were collected by filtration, dried, and dissolved in 300 ml of acetonitrile. Thereto were added 27.9 g of triethylamine and 27.9 of triphenylmethyl chloride, followed by stirring at 60"C for 1.5 hours. The reaction mixture was concentrated. To the concentrate was added 200 ml of methanol. The resulting crystals were collected by filtration to obtain 40.0 g (yield: 78.9%) of a title compound as colorless crystals.
(2) Production of 5-(4-hydroxybenzyl)-3-triphenyl
methylthiazolidine-2,4-dione
This step was conducted in the same manner as in (3) of Example 1.
The overall yield of (1) to (2) was 67.1%.
Comparative Example 1 (1) Production of 5- (4-acetoxybenzyl )thiazolidine- 2 ,4-dione In a 1,000-ml autoclave were placed 12 g of 5-(4-acetoxybenzylidene)thiazolidine-2,4-dione, 500 ml of acetic acid and 12 g of 10% palladium-carbon (a catalyst). Hydrogen gas was introduced into the autoclave at 300C at atmospheric pressure. Stirring was conducted for 5 hours. The reaction mixture was filtered to remove the catalyst. To the filtrate was added toluene, and the mixture was subjected to azeotropic distillation to remove acetic acid together with toluene. To the distillation residue were added toluene and hexane. The resulting crystals were collected by filtration to obtain 11.0 g (91.0%) of a title compound as colorless crystals.
(2) Production of 5-(4-acetoxybenzyl)-3-triphenyl
methylthiazolidine-2,4-dione
To 100 ml of dichloromethane were added 10 g of the 5-(4-acetoxybenzyl)thiazolidine-2,4-dione obtained in above (1), 3.81 g of triethylamine and 10.51 g of triphenylmethyl chloride. Stirring was conducted at room temperature for 3 hours. To the reaction mixture were added ethyl acetate and water. The organic layer was separated, washed with a saturated aqueous sodium chloride solution, and dried on anhydrous sodium sulfate. The desiccant was removed by filtration. The filtrate was subjected to distillation to remove the solvent. The resulting crystals were washed with a hexane-ethyl acetate mixed solvent to obtain 8.98 g (yield: 47.0%) of a title compound as colorless crystals.
(3) Production of 5-(4-hydroxybenzyl)-3-triphenyl
methylthiazolidine-2,4-dione
To 70 ml of toluene was added 7.61 g of the 5 (4-acetoxybenzyl ) -3-triphenylmethylthiazolidine-2, 4- dione obtained in above (2). Thereto were dropwise added, with ice-cooling, 2.89 g of a methanol solution containing 28% of sodium methoxide and 10 ml of methanol. The mixture was stirred at room temperature for 3 hours. To the reaction mixture was added 1 N hydrochloric acid for adjustment to pH 4. Extraction with ethyl acetate was conducted. The extract was washed with water and dried on anhydrous sodium sulfate.
The desiccant was removed by filtration. The filtrate was subjected to distillation to remove the solvent.
The resulting crystals were washed with hexane to obtain 5.93 g (85.0%) of a title compound as colorless crystals.
The overall yield of (1) to (3) was 36.4%.
Claims (13)
1. A process for producing 5-(4-hydroxybenzyl)-3triphenylmethylthiazolidine-2,4-dione via a acyloxybenzyl)thiazolidine-2,4-dione, which process comprises:
(a) a first step of protecting the phenolic hydroxyl group of 5- ( 4-hydroxybenzyl )thiazolidine-2, 4- dione with an acyl group,
(b) a second step of reacting the 5-(4acyloxybenzyl)thiazolidine-2,4-dione represented by the following general formula (1) obtained in the above first step, with triphenylmethyl chloride:
(wherein R1 is an alkyl group having 1-3 carbon atoms or a phenyl group), and
(c) a third step of removing the acyl group of the 5- ( 4-acyloxybenzyl ) -3-triphenylmethylthiazolidine- 2,4-dione represented by the following general formula (2) obtained in the above second step:
(wherein R1 has the same definition as given above).
2. A process according to Claim 1, wherein the 5 (4-hydroxybenzyl)thiazolidine-2,4-dione used in the first step is obtained by reducing a condensate between 4-hydroxybenzaldehyde and thiazolidine-2,4-dione.
3. A process according to Claim 1 or 2, wherein in the first step, the protection of the phenolic hydroxyl group of 5- ( 4-hydroxybenzyl )thiazolidine-2, 4- dione with an acyl group is conducted using an acid anhydride or an acid chloride in the presence of pyridine or a tertiary amine represented by the following general formula (3):
(wherein R2, R3 and R4 may be the same or different and are each an alkyl group of 1-3 carbon atoms or a phenyl group, and R3 and R4may form a ring together).
4. A process according to any of Claims 1 to 3, wherein in the second step, the reaction of the 5-(4acyloxybenzyl)thiazolidine-2,4-dione with triphenylmethyl chloride is conducted in the presence of pyridine or a tertiary amine represented by the above-mentioned general formula (3).
5. A process according to Claim 4, wherein the tertiary amine is used in an amount of at least 1.5 equivalents relative to the 5-(4-acyloxybenzyl)thiazolidine-2,4-dione.
6. A process according to any of Claims 1 to 5, wherein in the third step, the removal of the acyl group is conducted in the presence of a sodium alkoxide having 1 to 3 carbon atoms in an alcohol solvent having 1 to 3 carbon atoms.
7. A process according to any of Claims 1 to 6, wherein in the first step, the protection of the phenolic hydroxyl group with an acyl group is conducted using an acid anhydride or an acid chloride in the presence of an organic solvent.
8. A process according to Claim 7, wherein the organic solvent is an ester type solvent or a nitrile type solvent.
9. A process according to Claim 8, wherein the organic solvent is methyl acetate, ethyl acetate or acetonitrile.
10. A process according to any of Claims 1 to 7, wherein the R1 of the general formula (1) and the general formula (2) is a methyl group.
11. A process according to Claim 3 or 4, wherein the R1 of the general formula (1) and the general formula (2) is a methyl group and the R2, R3 and R4 of the general formula (3) are each an ethyl group.
12. A process according to Claim 4, wherein the
R2, R3 and R4 of the general formula (3) are each an ethyl group and the amount of the tertiary amine used is at least 2 equivalents relative to the 5-(4-acyloxybenzyl)thiazolidine-2,4-dione represented by the general formula (1).
13. A process according to Claim 6, wherein the sodium alkoxide having 1 to 3 carbon atoms is sodium methoxide and the alcohol having 1 to 3 carbon atoms is methanol.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10397197 | 1997-04-08 | ||
| JP12013097A JPH10338679A (en) | 1997-04-08 | 1997-04-24 | Production of thiazolidine derivative |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| GB9807505D0 GB9807505D0 (en) | 1998-06-10 |
| GB2324089A true GB2324089A (en) | 1998-10-14 |
| GB2324089B GB2324089B (en) | 2001-08-15 |
Family
ID=26444537
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB9807505A Expired - Fee Related GB2324089B (en) | 1997-04-08 | 1998-04-07 | Process for production of thiazolidine derivative |
Country Status (2)
| Country | Link |
|---|---|
| JP (1) | JPH10338679A (en) |
| GB (1) | GB2324089B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003029251A1 (en) * | 2001-09-28 | 2003-04-10 | Biocon Limited | Novel process for the synthesis of thiazolidinedione derivatives |
| WO2009148195A1 (en) * | 2008-06-02 | 2009-12-10 | Daebong Ls, Ltd. | 5-(4-hydroxybenzyl)thiazolidine-2,4-dione as intermediate for synthesis of thiazolidinedione based compounds and process for preparing the same |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0543662A2 (en) * | 1991-11-20 | 1993-05-26 | Sankyo Company Limited | Aromatic amino-alcohol derivatives having anti-diabetic and anti-obesity properties, their preparation and their therapeutic uses |
| EP0549366A1 (en) * | 1991-12-26 | 1993-06-30 | Sankyo Company Limited | Thiazolidine compounds containing a quinone group, their preparation and their therapeutic uses |
-
1997
- 1997-04-24 JP JP12013097A patent/JPH10338679A/en active Pending
-
1998
- 1998-04-07 GB GB9807505A patent/GB2324089B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0543662A2 (en) * | 1991-11-20 | 1993-05-26 | Sankyo Company Limited | Aromatic amino-alcohol derivatives having anti-diabetic and anti-obesity properties, their preparation and their therapeutic uses |
| EP0549366A1 (en) * | 1991-12-26 | 1993-06-30 | Sankyo Company Limited | Thiazolidine compounds containing a quinone group, their preparation and their therapeutic uses |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003029251A1 (en) * | 2001-09-28 | 2003-04-10 | Biocon Limited | Novel process for the synthesis of thiazolidinedione derivatives |
| WO2009148195A1 (en) * | 2008-06-02 | 2009-12-10 | Daebong Ls, Ltd. | 5-(4-hydroxybenzyl)thiazolidine-2,4-dione as intermediate for synthesis of thiazolidinedione based compounds and process for preparing the same |
Also Published As
| Publication number | Publication date |
|---|---|
| GB2324089B (en) | 2001-08-15 |
| JPH10338679A (en) | 1998-12-22 |
| GB9807505D0 (en) | 1998-06-10 |
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| 732E | Amendments to the register in respect of changes of name or changes affecting rights (sect. 32/1977) | ||
| PCNP | Patent ceased through non-payment of renewal fee |
Effective date: 20050407 |