Dimethylformamide → 3-Bromo-5-ethyl-2-fluorobenzaldehyde

Temperature

-10 °C

To a solution of diisopropylamine (0.449 mL, 3.20 mmol) in 10 mL THF at −15° C., was added BuLi (1.6M, 1.85 mL, 2.95 mmol). The mixture was stirred 10 min at −10° C., then was cooled to −78° C. A solution of 2-bromo-4-ethyl-1-fluorobenzene (228.1) in 2 mL THF was added, then the mixture was stirred at −70° C. for 25 min. DMF (0.381 mL, 4.92 mmol) was added, then the reaction was removed from the cooling bath and stirred 30 min. The reaction was quenched with sat. NH4Cl, then was diluted with EtOAc. The organic phase was washed with H2O and brine, dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography (0-20% EtOAc/hexanes gradient) to afford 429 mg of Intermediate 398.1 at a colorless solid. LCMS (2 min gradient) RT=1.70 min, 231.0 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 1.25 (t, J=7.69 Hz, 3H) 2.67 (q, J=7.47 Hz, 2H) 7.61-7.66 (m, 2H) 10.33 (s, 1H).

1. temperaturewas cooled to −78° C
2. stirringthe mixture was stirred at −70° C. for 25 min
3. customthe reaction was removed from the cooling bath
4. stirringstirred 30 min
5. customThe reaction was quenched with sat. NH4Cl
6. additionwas diluted with EtOAc
7. washThe organic phase was washed with H2O and brine
8. dry with materialdried (Na2SO4)
9. concentrationconcentrated
10. customThe crude product was purified by flash chromatography (0-20% EtOAc/hexanes gradient)

ORD record

ord-c9f27ee08c1948c2a71bc67e49190481

Source dataset

uspto-grants-2009_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07576098B2