3-(2-bromoacetyl)benzoic Acid → 4-(3-Carboxyacetyl-phenyl)-thiazole-2-carboxylic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

The 4-(3-carboxyacetyl-phenyl)-thiazole-2-carboxylic acid ethyl ester was prepared from 4-(3-chlorocarbonyl-phenyl)-thiazole-2-carboxylic acid ethyl ester [prepared by the following sequence: i.) A mixture of 3-(2-bromo-acetyl)-benzoic acid [CAS-no. 62423-73-8] (2.43 g) and ethyl thiooxamate [CAS-no. 16982-21-1] (1.6 g) in THF (40 mL) was heated to 60° C. for 4 h and then partitioned between EtOAc and brine. The organic layer was dried and evaporated and the residue was crystallized from EtOAc/hexane to give 4-(3-carboxy-phenyl)-thiazole-2-carboxylic acid ethyl ester (2.2 g) as off-white crystals, mp 225-228° C. ii.) This carboxylic acid (2.1 g) was heated with thionyl chloride in toluene and the resulting carboxylic acid chloride was used directly in the next step.] (2.24 g) and bis(trimethylsilyl)malonate with n-BuLi in ether at −60° C. to 0° C. according to general procedure K (method c2). The crude material was transformed into the title compound by stirring in isopropenyl acetate and conc. H2SO4 according to general procedure L (method a). Obtained as yellow oil (2.7 g).

Provenance & Evidence