Nitrogen → HCID 59536649, compound

Participants

Reaction Steps

Charge a 200 mL round bottom flask equipped with a Claisen adaptor, thermal couple and N2 inlet with (S)-1-benzyl-3-((S)-1-hydroxy-3-methylbutyl)-pyrrolidine (5.69 g, 23 mmoles) and DMA (58 mL). Add NaH (1.29 g, 32.2 mmoles) in one portion with stirring and stir at room temperature for 1 hour. Add 6-chloro-3-fluoro-2-methylpyridine (3.52 g, 24.15 mmoles) in one portion with stirring and then stir at room temperature for 24 hours. Quench the reaction mixture with H2O (120 mL) and extract with MTBE (120 mL). Wash the organic layer with H2O (2×60 mL), followed by brine (60 mL), and then dry over Na2SO4. Filter, concentrate, and then purify the crude material (in toluene) by loading onto silica (225 g, wet with toluene) and eluting with the following: hexanes (2×500 mL), 15% MTBE/hexanes (16×500 mL), 50% MTBE/hexanes (8×500 mL). Concentrate the appropriate fractions to give (S)-1-benzyl-3-((S)-1-(6-chloro-2-methyl-3-pyridyloxy)-3-methylbutyl)-pyrrolidine as a light yellow oil (5.77 g, 15.47 mmoles, 67% yield, purity >98%). 1H NMR (300 MHz, CDCl3) δ 7.38-7.20 (m, 5H), 7.06 (s, 2H), 4.32-4.20 (m, 1H), 3.68-3.48 (m, 2H) 2.78-2.64 (m, 2H), 2.64-2.30 (m, 2H), 2.42 (s, 3H), 2.28-2.20 (m, 1H), 2.05-1.85 (m, 1H), 1.82-1.52 (m, 4H), 1.48-1.34 (m, 1H), 0.92 (d, 3H, J=6.45 Hz), 0.88 (d, 3H, J=6.45 Hz). LC/MS=373.2 (M), 375.3 (M+2).

Provenance & Evidence