Dimethylformamide → N-(5-Fluoro-2-formylphenyl)pivalamide

Temperature

-78 °C

N-(2-bromo-5-fluorophenyl)pivalamide(2.4 g, 8.75 mmol)) was dissolved in THF (30 mL) at room temperature, and the colorless solution was cooled to −78° C., followed by fast dropwise addition of t-BuLi (10.3 mL, 1.7M in heptane, 17.4 mmol) under N2 over 10 min. The resulting yellow solution was continued stirring at −78° C. for 1 hr, followed by dropwise addition of DMF (2.7 mL, 35.0 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), extracted with Et2O (2×150 mL). The combined 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 (1.03 g, 53% yield); 1H NMR (400 MHz, CDCl3) δ ppm 1.30 (s, 9 H), 6.80-6.86 (m, 1 H), 7.63 (dd, J=8.56, 6.04 Hz, 1 H), 8.53 (dd, J=12.21, 2.39 Hz, 1 H), 9.83 (s, 1 H), 11.54 (s, 1 H); Mass spec. 224.16(MH+), Calc. for C12H14FNO2 223.1.

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. extractionextracted with Et2O (2×150 mL)
4. washThe combined organic phase was washed with brine (30 mL)
5. dry with materialdried over MgSO4
6. concentrationconcentrated on rotary vacuum
7. custompurified on flash chromatography
8. washeluting with 25˜50% EtOAc/hexanes (1400 mL)

ORD record

ord-87554d3af1e64b2ab5ad3b722a272224

Source dataset

uspto-grants-2008_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07384930B2