Sodium hydride → 3-((1-methyl-2-(R)-pyrrolidinyl)methoxy)-5-trifluoromethylpyridine

Participants

Reaction Steps

(R)-1-methyl-2-pyrrolidinemethanol (Aldrich Chemical Co.) was dissolved in 8 mL of DMF and stirred under N2, then 240 mg of NaH (80% dispersion in mineral oil) was added. The reaction mixture was stirred fifteen minutes, and 363 mg of 3-chloro-5-trifluoromethylpyridine (2.0 mmol) was added. The reaction mixture was stirred at 50° C. for 16 hours. The volatiles were removed under vacuum, and the residue was purified by chromatography on silica gel, eluting with 2:1 ethyl acetate:hexane to give 336 mg of the title product. MS (DCI/NH3) m/e: 261 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ: 8.50 (d, J=0.6 Hz, 1H), 8.49 (d, J=3.0 Hz, 1H), 7.41 (dd, J=0.6, 3.0 Hz, 1H), 4.12-3.96 (m, 2H), 3.21-3.10 (m, 1H), 2.80-2.65 (m, 1H), 2.51 (s, 3H), 2.44-2.30 (m, 1H), 2.13-1.73 (m, 4H).

Provenance & Evidence