Diisopropylamine → 2-(4-t-Butoxy-5-fluoro-3-methyl-2-pyridinyl)-2-cyclopropylacetaldehyde

Participants

Reaction Steps

To a solution of LDA (1.20 mmol, prepared from diisopropylamine (0.16 mL) and n-BuLi (2.5M in hexanes, 0.48 mL) in THF (2.0 mL) at 0° C. was added N-(2-cyclopropyl-ethylidene)cyclohexylamine (1.24 mmol, from step 3a) dropwise, and the reaction mixture was warmed to room temperature and stirred for 15 minutes. To this solution was added 4-t-butoxy-5-fluoro-3-methylpyridine (0.10 mL, 0.50 mmol) in THF (0.5 mL) dropwise and the mixture was stirred for 3.5 hours. The reaction was then quenched with acetic acid (1M, 3 mL), diluted with hexanes (20 mL) and dilute acetic acid (1M, 20 mL), and stirred vigorously for 1 hour. The organic layer was separated, washed with water, saturated NaHCO3 and brine, dried (MgSO4) and concentrated. The residue was purified by chromatography on silica gel, eluting with 5% to 15% ethyl acetate in hexanes, to afford the title compound (0.098 g, 75% yield) as an oil. MS 266 (M+H)+ ; 1H NMR (CDCl3) δ0.19-0.32 (m, 2H), 0.52-0.75 (m, 2H), 1.42 (d, 9H, J=1.1 Hz), 1.42-1.60 (m, 1H), 2.20 (s, 3H), 3.16 (dd, 1H, J=2.6 Hz, J =8.8 Hz), 8.29 (d, 1H, J=2.2 Hz), 9.86 (d, 1H, J=2.6 Hz).

Provenance & Evidence