Dimethylformamide → 4-Chloro-2-fluoro-3-methoxybenzaldehyde

Temperature

-78 °C

1-Bromo-4-chloro-2-fluoro-3-methoxybenzene (23.7 g, 99 mmol, see U.S. Pat. No. 7,300,907 for preparation) was dissolved in dry diethyl ether and cooled to −78° C. 2.5M n-Butyllithium in hexanes (44 mL, 110 mmol) was added in portions, keeping the temperature below −70° C. during the addition. DMF (15.5 mL, 200 mmol) was then added in portions, keeping the temperature below −60° C. The reaction mixture was then allowed to warm to ambient temperature and quenched with water. The organic phase was dried and concentrated. The product was purified by flash chromatography on silica gel (hexane/ethyl acetate gradient) to yield the title compound in sufficient purity for subsequent reactions (11.4 g, 61% yield): 1H NMR (CDCl3) δ 10.32 (s, 1H), 7.55 (m, 1H), 7.3 (m, 1H), 4.05 (d, 3H).

1. custom7,300,907 for preparation)
2. customthe temperature below −70° C.
3. additionduring the addition
4. customthe temperature below −60° C
5. temperatureto warm to ambient temperature
6. customquenched with water
7. customThe organic phase was dried
8. concentrationconcentrated
9. customThe product was purified by flash chromatography on silica gel (hexane/ethyl acetate gradient)

ORD record

ord-f52636974f6f4531aa98662de596d049

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08426591B2