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)

Safety Information

HS Code 

2934100090

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(161798-01-2)Related Product Information

• Febuxostat
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