p-Toluenesulfonic acid → [Rac]-2-[1-methyl-3-oxo-3-phenyl-(z)-propenylamino]-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-yl}-propionic acid ethyl ester

Participants

Reaction Steps

0.334 g (0.75 mmol) [rac]-2-Amino-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-yl}-propionic acid ethyl ester (prepared from 4-[2-(7-bromomethyl-benzo[b]thiophen-4-yloxy)-ethyl]-5-methyl-2-phenyl-oxazole [PCT Int. Appl. (2001) WO01/79202] and N-(diphenylmethylene)glycine ethyl ester in analogy to the sequence described in examples 15 a] and 15 b]) and 0.161 g (0.97 mmol) benzoylacetone were dissolved in 25 ml of toluene. Then, 0.21 ml (1.5 mmol) triethylamine and 0.026 g (0.15 mmol) 4-toluene sulfonic acid were added and the reaction mixture was heated at reflux for 2 hours. After removing the solvent under reduced pressure, the residue was diluted in water/sodium hydrogen carbonate solution and the reaction mixture was extracted with dichloromethane. The combined organic phases were dried over MgSO4 and evaporated. Purification of the residue by flash-chromatography (silica gel, eluent: gradient of hexane and ethyl acetate) gave 0.38 g (85%) [rac]-2-[1-methyl-3-oxo-3-phenyl-(Z)-propenylamino]-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-yl}-propionic acid ethyl ester as light yellow oil.

Provenance & Evidence