2,2,2-Trifluoroethanol → 2-Amino-4,6-bis(2,2,2-trifluoroethoxy)pyrimidine

Participants

Reaction Conditions

Reaction Steps

To a solution of trifluoroethanol (9.0 mL, 125 mmol) in anhydrous THF (100 mL) at 0° C. in a 3-neck round bottom flask under an atmosphere of dry N2 was added NaH (4.8 g, 120 mmol, 60% dispersion in mineral oil) over ca. 1 min. After gas evolution ceased and the solution became clear (ca. 20 min), 2-amino-4,6-dichloropyrimdine (8.2 g, 50 mmol) was added. The flask was fitted with a reflux condenser and heated to 62° C. overnight (ca. 15 h). An NMR of a quenched aliquot from the reaction mixture demonstrated the reaction was complete. After the reaction mixture was cooled to ambient temperature it was quenched by addition of 1 N HCl and diluted with EtOAc. The separated organic layer was washed with brine, sat. aq. NaHCO3 and then brine. After drying over MgSO4, filtering and concentrating, the oil thus obtained was dissolved in acetonitrile and washed with hexanes (2×, to remove mineral oil) and concentrated to afford the desired amine as an orange oil (13.9 g, 96% yield): Kugelrohr distillation (high vacuum, 90° C. bath temperature, ice bath for receiving flask) afforded the product as a white solid: m.p. 34-35° C.; 1H NMR (CDCl3) δ 5.69 (s, 1H), 4.95 (br s, 2H), 4.69 (q, 4H, J=8.1 Hz); GCMS (EI, 70 eV) m/z 291 (M+).

Provenance & Evidence