Dimethylformamide → N-(6-Fluoro-3-formylpyridin-2-yl)pivalamide

Participants

Reaction Conditions

Reaction Steps

N-(6-fluoropyridin-2-yl)pivalamide(1.67 g, 8.5 mmol) was dissolved in THF (15 mL) at room temperature, and the colorless solution was cooled to −78° C., followed by dropwise addition of t-BuLi (10.3 mL, 1.7M in heptane, 17.4 mmol) under nitrogen gas over 10 min. The resulting yellow solution was continued stirring at −78° C. for 3 hr, followed by dropwise addition of DMF (2.0 mL, 25.5 mmol) over 5 min. The light yellow solution was stirred for additional 30 min at −78° C. Thus the mixture was quenched with saturated NH4Cl (30 mL), partitioned between H2O/EtOAc (100 mL/100 mL). After separation, the organic phase was washed with brine (30 mL), dried over MgSO4, concentrated on rotary vacuum, and purified on flash chromatography eluting with 25˜50% EtOAc/hexanes (1400 mL) to afford an expected product, as a white solids (343 mg, 18% yield), plus the recovered starting material (622 mg); 1H NMR (400 MHz, CDCl3) δ ppm 1.23-1.30 (s, 9 H), 8.12 (s, 1 H), 8.18-8.27 (m, 2 H), 10.13 (s, 1 H); Mass spec. 225.13 (MH+), Calc. for C11H13FN2O2224.1.

Provenance & Evidence