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| | Ethyl 2-(3-Formyl-4-hydroxyphenyl)-4-methylthiazole-5-carboxylate Basic information |
| Product Name: | Ethyl 2-(3-Formyl-4-hydroxyphenyl)-4-methylthiazole-5-carboxylate | | Synonyms: | ethyl 2-(3-formyl-4-hydroxyphenyl)-4-methyl thiazole-5-carboxylate;2-(3-Formyl-4-hydroxy-phenyl)-4-methyl-thiazole-5-carboxylic acid ethyl ester;Thiazolecarboxylicacid,2-(3-forMyl-4-hydroxyphenyl)-4-Methyl-,ethylester;5-carboxylato-1-ethyl-2-(3-forMyl-4-hydroxyphenyl)-4-Methyl-1H-1$l^{4},3-thiazol-1-yl;Ethyl 2-(3-forMyl-4-hydroxyphenyl)-4-Methyl-5-Thiazolecarboxylate;5-carboxylato-1-ethyl-2-(3-forMyl-4-h;ETHYL 2-(3-FORMYL-4-HYDROXYPHENYL)-4-METHYL-1,3-THIAZOLE-5-CARBOXYLATE;Febuxostat-23 | | CAS: | 161798-01-2 | | MF: | C14H13NO4S | | MW: | 291.32 | | EINECS: | 692-179-2 | | Product Categories: | Febuxostat intermediate;161798-01-2 | | Mol File: | 161798-01-2.mol |  |
| | Ethyl 2-(3-Formyl-4-hydroxyphenyl)-4-methylthiazole-5-carboxylate Chemical Properties |
| Melting point | 116 °C | | Boiling point | 446.7±55.0 °C(Predicted) | | density | 1.335 | | storage temp. | under inert gas (nitrogen or Argon) at 2-8°C | | solubility | DMSO (Slightly), Methanol (Slightly) | | form | Solid | | pka | 6.81±0.20(Predicted) | | color | Pale Yellow to Yellow | | InChI | InChI=1S/C14H13NO4S/c1-3-19-14(18)12-8(2)15-13(20-12)9-4-5-11(17)10(6-9)7-16/h4-7,17H,3H2,1-2H3 | | InChIKey | NJRGQNNSIAFIJC-UHFFFAOYSA-N | | SMILES | S1C(C(OCC)=O)=C(C)N=C1C1=CC=C(O)C(C=O)=C1 | | CAS DataBase Reference | 161798-01-2(CAS DataBase Reference) |
| | Ethyl 2-(3-Formyl-4-hydroxyphenyl)-4-methylthiazole-5-carboxylate Usage And Synthesis |
| Description | Ethyl 2-(3-formyl-4-hydroxyphenyl)-4-methyl thiazole-5-carboxylate is a pharmaceutical intermediate used in the preparation of the xanthine oxidase inhibitor febuxostat, which is used in the treatment of hyperuricaemia and gout. It is also used in the synthesis of novel thiazolyl α-aminophosphonates. | | Chemical Properties | Yellow or yellow powder | | Uses | Ethyl 2-(3-Formyl-4-hydroxyphenyl)-4-methylthiazole-5-carboxylate is a product prepared via reaction 4-Hydroxybenzene-1-benzothiomide with ethyl-2-chloro acetoacetate. An antibacterial agent and antifungal activity against C.albicans. | | Synthesis | The general procedure for the synthesis of ethyl 2-(3-formyl-4-hydroxyphenyl)-4-methylthiazole-5-carboxylate from ethyl 2-(4-hydroxyphenyl)-4-methylthiazole-5-carboxylate and urotropine was as follows: 120 kg of polyphosphoric acid was added to a clean and dry 200 L reactor, stirred and heated to 40-50°C. After stirring, 20 kg ( 76.0 mol) ethyl 2-(4-hydroxyphenyl)-4-methyl-5-thiazolecarboxylate and 11 kg (76.3 mol) hexamethylenetetramine (HMTA) were added sequentially. After the addition was completed, the reaction mixture was heated to 93°C for 3 hours. After completion of the reaction, the reaction solution was slowly poured into dilute aqueous glacial acetic acid solution for hydrolysis for 20 min. The reaction mixture was extracted with 300 L of ethyl acetate in three portions and the organic phases were combined. To the organic phase, 10 kg of anhydrous sodium sulfate was added for drying, and after filtration, the filtrate was concentrated under reduced pressure to obtain 210 mg of ethyl acetate solvent. To the concentrate, 100 kg of water was added and stirred to induce crystallization, followed by centrifugal separation and drying, resulting in 18.0 kg of light yellow intermediate product in 81.3% yield. The intermediate 2-(3-formyl-4-hydroxyphenyl)-4-methyl-5-thiazolecarboxylic acid ethyl ester was tested to be 99.4%, and the dicarboxylic acid impurity content was 0.008%. | | References | [1] Patent: CN106366048, 2017, A. Location in patent: Paragraph 0007; 0008; 0009; 0010; 0011; 0012
[2] Patent: WO2012/14117, 2012, A1. Location in patent: Page/Page column 12
[3] Patent: WO2012/131590, 2012, A1. Location in patent: Page/Page column 15; 21-23
[4] Patent: WO2012/168948, 2012, A2. Location in patent: Page/Page column 10-11
[5] Letters in Organic Chemistry, 2015, vol. 12, # 3, p. 217 - 221 |
| | Ethyl 2-(3-Formyl-4-hydroxyphenyl)-4-methylthiazole-5-carboxylate Preparation Products And Raw materials |
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