Chloroacetic Acid → 6-(Trifluoromethyl)uracil

Participants

Reaction Steps

Compound XXVI was prepared according to the procedure of Kaiser, C. and Burger, A. J Org. Chem. 1959, 24, 113. 6-Trifluoromethyl-2-thiouracil (XXV) [Gershon, H et al. J. Het. Chem. 1983, 20(1), 219] (15 g, 76 mmol) was mixed with H2O (150 mL), chloroacetic acid (14.4 g, 152 mmol) was added and the mixture was heated to reflux. After 1 hr at reflux all the solids had dissolved. Analysis of the reaction mixture by LC-MS after 4 hrs at reflux indicated complete alkylation of the sulfur. The reaction was cooled to room temperature. Upon cooling a solid precipitated. To the mixture was added concentrated HCl (50 mL, 38%) and the mixture was heated to reflux. After 4 hrs at reflux the heat was removed, the solution cooled to room temperature and allowed to stir for 18 hrs. The solids were filtered and dried in a vacuum oven (50° C.) overnight to afford 6-trifluoromethyluracil (XXVI) as a white solid (8.8 g, 64%): m.p. 225-227° C.; 1H NMR (DMSO-d6) δ 12.1 (s, 1H), 11.6 (s, 1H), 6.1 (s, 1H); ESI/MS 179 (M−H).

Provenance & Evidence