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

2,2,2-Trifluoroethanol (2.2 mL, 30 mmol) was slowly added to a suspension of NaH (1.5 g, 36 mmol, 60% dispersion in mineral oil) in anhydrous THF (50 mL) under an N2 atmosphere. To the resulting mixture was added a solution of 2-amino-4-chloro-6-trifluoromethylpyrimidine (5.0 g, 25 mmol; for preparation see: Giner-Sorolla, A. and Bendich, A. J. Am. Chem. Soc. 1957, 80, 5744 and Gershon, H. et al. J. Het. Chem. 1983, 20, 219) in anhydrous THF (50 mL). The resulting mixture was stirred 18 h at room temperature and the solvent evaporated. The resulting residue was partitioned between CH2Cl2 (200 mL) and H2O (200 mL). The organics separated, dried over MgSO4, filtered and evaporated to afford 2-amino-4-(2,2,2-trifluoroethoxy)-6-trifluoromethyl-pyrimidine as a tan solid (4.9 g, 74% yield): m.p. 108-110° C.; 1H NMR (CDCl3) δ 6.54 (s, 1H), 5.53 (bs, 2H), 4.76 (q, 2H, J=8.2 Hz); GCMS (EI, 70 eV) m/z 261 (M+).

1. customfor preparation
2. customthe solvent evaporated
3. customThe resulting residue was partitioned between CH2Cl2 (200 mL) and H2O (200 mL)
4. dry with materialThe organics separated, dried over MgSO4
5. filtrationfiltered
6. customevaporated

ORD record

ord-939b725569034c919c0a801e4056b59a

Source dataset

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08455649B2