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

Temperature

-78 °C

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

1. stirringThe light yellow solution was stirred for additional 30 min at −78° C
2. customThus the mixture was quenched with saturated NH4Cl (30 mL)
3. custompartitioned between H2O/EtOAc (100 mL/100 mL)
4. customAfter separation
5. washthe organic phase was washed with brine (30 mL)
6. dry with materialdried over MgSO4
7. concentrationconcentrated on rotary vacuum
8. custompurified on flash chromatography
9. washeluting with 25˜50% EtOAc/hexanes (1400 mL)

ORD record

ord-42a44a94347545a3b109cce37ddb8b06

Source dataset

uspto-grants-2008_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07384930B2