Dimethylformamide → 3-Chloro-5-methoxybenzaldehyde

Temperature

-10 °C

To a mixture of dichloroanisole (60 mmol, 10.62 g), Mg (66 mmol, 1.60 g) and THF (30 ml) was added 1,2-dibromoethane (6 mmol, 1.13 g). The mixture was stirred until bubbles of gas started to evolve (2-3 min), and then heated to reflux for 2.5 h. The resulting dark brown mixture was cooled to −10° C. on an acetone-ice bath and DMF (90 mmol, 7 ml) was added slowly. After 20 min the ice-bath was removed, the mixture was stirred for 3 h and subsequently quenched with NHrCl (10% w/w in water, 100 ml). The product mixture was extracted with DCM (4×50 ml), the organic phase washed with water, then brine and dried (MgSO4). Filtration and evaporation under reduced pressure gave a red liquid residue, which was purified by means of flash chromatography (silica, pentane/ether gradient. 5-30%) to provide the title compound (4.60 g, 45%) as a clear liquid. 1H NMR (DMSO, 300 MHz) δ 3.84 (s, 3H), 7.16 (s, 1H), 7.25 (s, 1H), 7.43 (s, 1H) and 9.92 (s, 1H).

1. custom(2-3 min)
2. temperatureheated
3. temperatureto reflux for 2.5 h
4. customAfter 20 min the ice-bath was removed
5. stirringthe mixture was stirred for 3 h
6. customsubsequently quenched with NHrCl (10% w/w in water, 100 ml)
7. extractionThe product mixture was extracted with DCM (4×50 ml)
8. washthe organic phase washed with water
9. dry with materialbrine and dried (MgSO4)
10. filtrationFiltration and evaporation under reduced pressure
11. customgave a red liquid residue, which
12. customwas purified by means of flash chromatography (silica, pentane/ether gradient. 5-30%)

ORD record

ord-ee01078594e14c90ac4b80fe9d4c537e

Source dataset

uspto-grants-2010_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07799947B2