Ethyl 2-chloroacetoacetate → Ethyl 2-amino-4-methylthiazole-5-carboxylate

Participants

Reaction Steps

A mixture of ethyl 2-chloroacetoacetate (50 g, 0.30 mol, Aldrich) and thiourea (45.6 g, 0.60 mol) in 400 mL of absolute ethanol was heated to reflux. After refluxing overnight the reaction mixture was allowed to cool to room temperature and then concentrated to half the original volume in vacuo. The remaining ethanol solution was poured into H2O (1L) and made basic (pH 10) with 2N NaOH. An off-white solid precipitated immediately. The mixture was stirred for ~10 minutes and then the solid was removed by vacuum filtration and dried to give 54.75 g (98% yield) of the desired product as a white solid: 1H NMR (CDCl3) 67 5.5 (bs, 2H), 4.25 (q, 2H), 2.5 (s, 3H), 1.35 (t, 3H).

Provenance & Evidence