Dimethylformamide → 4-(1,1-Difluoroethyl)-2-fluorobenzaldehyde

Temperatur

-78 °C

To a solution of 1-bromo-4-(1,1-difluoroethyl)-2-fluorobenzene (2.1 g, 8.79 mmol) in THF (30.3 mL) was added n-butyllithium (1.6M in hexanes, 5.60 mL) over ˜20 min at −78° C. The mixture was stirred for 30 min at −78° C. and DMF (1.02 mL, 13.18 mmol) was added dropwise over ˜4 min. Stirring was continued for 1 hr, the mixture was diluted/quenched with 1N aqueous HCl/MeOH (2/1, 15 mL) and allowed to warm to room temperature. The reaction mixture was diluted further with water (50 mL) and extracted with diethylether (2×50 mL). The combined organic layers were washed with 1N aqueous sodium hydroxide solution (50 mL) and brine (100 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography [SiO2, 40 g, heptane/ethyl acetate] providing 4-(1,1-difluoroethyl)-2-fluorobenzaldehyde (699 mg) as a dark yellow, volatile oil, which was contaminated with 1-bromo-4-(1,1-difluoroethyl)-2-fluorobenzene. 1H NMR (400 Mhz, CDCl3) δ ppm 10.40 (s, 1H), 7.95 (t, J=7.4 Hz, 1H), 7.39-7.47 (m, 2H), 7.35 (d, J=10.6 Hz, 1H), 1.94 (t, J=18.2 Hz, 4H) 7.73 (dd, J=7.2, 8.1 Hz, 1H).

1. stirringStirring
2. waitwas continued for 1 hr
3. customthe mixture was diluted/quenched with 1N aqueous HCl/MeOH (2/1, 15 mL)
4. temperatureto warm to room temperature
5. additionThe reaction mixture was diluted further with water (50 mL)
6. extractionextracted with diethylether (2×50 mL)
7. washThe combined organic layers were washed with 1N aqueous sodium hydroxide solution (50 mL) and brine (100 mL)
8. dry with materialdried over magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customThe crude material was purified by column chromatography [SiO2, 40 g, heptane/ethyl acetate]

ORD-Eintrag

ord-8610bf48d95d40f38696a58d95f1cfbb

Quelldatensatz

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09434719B2