Water → 3-(3-Benzyloxy-4-fluoro-phenylamino)-but-2-enoic acid ethyl ester

Participants

Reaction Steps

92.7 g (0.43 mol) of 3-Benzyloxy-4-fluoro-phenylamine, 57 ml (0.45 mol) of ethyl acetoacetate and 0.81 g (4 mmol) of p-toluenesulfonic acid monohydrate in 370 ml of cyclohexane were heated at reflux for 3 h in the presence of a water separator funnel. The reaction mixture was cooled to RT, ACOEt (1 l) and saturated aqueous NaHCO3 solution (0.5 l) were added, the layers were separated and the organic layer once extracted with AcOEt (0.3 l). The combined organic layers were dried over magnesium sulfate and concentrated in vacuo to give 140 g (100%) of the desired 3-(3-benzyloxy-4-fluoro-phenylamino)-but-2-enoic acid ethyl ester as yellow-orange crystalline solid. Melting point: 79° C.-80° C.

Provenance & Evidence