Acetic acid, [2,3-dichloro-4-(1-oxobutyl)phenoxy]-, ethyl ester synthesis

Yield:-

Reaction Conditions:

with potassium carbonate in toluene; for 48 h;Reflux;

Steps:

2.1. General procedure for the preparation of ethacrynic acidand its analogues

General procedure: The synthesis of ethacrynic acid (IV-1) and its sevenanalogues (IV-2-8, Fig. 1) was accomplished by a threestepreaction shown in Scheme 1. The Friedel-Craftsacylation reaction of the phenol or the substituted phenolsI-1-4 (Scheme 1), respectively, with propanoyl chloride (n = 1) or butanoyl chloride (n = 2), respectively, wasperformed in the presence of powdered aluminiumchloride (AlCl3) in carbon disulfide, as recently describedby us [22]. Compounds II-1-8 were purified by flashcolumn chromatography on silica gel and consecutivelyrefluxed in acetone for 48 hours in the presence of 1.2equivalents of ethyl bromoacetate and two equivalentspotassium carbonate (K2CO3) to yield compounds III-1-8.In the third step, an aldol condensation reaction, compoundsIII-1-8 were refluxed in an ethanol/water (50/50)mixture for 24 hours in the presence of two equivalents offormaldehyde and 2.5 equivalents of K2CO3. CompoundsIV-1-8 were obtained by flash chromatography using ahexanes/ethyl acetate/methanol mixture as the eluent.

References:

Janser, Ingo;Vortolomei, Caitlyn M.;Meka, Ranjith K.;Walsh, Courtney A.;Janser, Romy F.J. [Comptes Rendus Chimie,2013,vol. 16,# 7,p. 660 - 664]