Methanol → 1-Chloro-2-fluoro-4-methoxy-5-nitrobenzene

To a suspension of potassium tert-butoxide (15.07 g, 134.3 mmol) in toluene (100 mL), and the appropriate alcohol, in this case methanol (3.80 g, 118.7 mmol), was added at 0° C. and stirred for 15 minutes. A solution of the appropriate 1-substituted 2,4-difluoro-5-nitrobenzene, in this case 1-chloro-2,4-difluoro-5-nitrobenzene (20.0 g, 103.3 mmol), in toluene (50 mL) was added at 0° C. and stirred for 5 hours at room temperature. Water (1000 mL) was added and the mixture was extracted with EtOAc (3×100 mL). The combined organic extracts were washed with water (150 mL), brine (150 mL), dried (Na2SO4) and concentrated under reduced pressure. The crude residue was purified by column chromatography on neutral silica gel using 5-10% EtOAc in hexane to give the title compound (11.0 g, 52%) as a solid.

1. stirringstirred for 5 hours at room temperature
2. extractionthe mixture was extracted with EtOAc (3×100 mL)
3. washThe combined organic extracts were washed with water (150 mL), brine (150 mL)
4. dry with materialdried (Na2SO4)
5. concentrationconcentrated under reduced pressure
6. customThe crude residue was purified by column chromatography on neutral silica gel using 5-10% EtOAc in hexane

ORD record

ord-03b81957356b46d3ac7b10cdf0ba4e2d

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08716287B2