Sodium Hydroxide → 3-bromo-5-nito-1-(difluoromethoxy)benzene

To a solution of 3-bromo-5-nitrophenol (3.1 g, 14.4 mmol) and powdered sodium hydroxide (0.63 g, 15.8 mmol) in DMF (14 mL), sodium chlorodifluoroacetate (4.4 g, 28.7 mmol) was added in five portions every 0.5 hour to the warmed reaction mixture at to 55° C. The reaction was maintained at to 55° C. for 1 day and then allowed to cool to room temperature. The reaction mixture was partitioned between EtOAc and water, the layers separated, and the aqueous portion was extracted (2×25 mL) EtOAc and the combined organic layers were washed with aqueous 1.0 M NaOH solution (3×25 mL), water (3×25 mL) and brine (50 mL). The organic layer was dried (MgSO4), and concentrated. The resulting residue was purified by flash chromatography (SiO2, 0-50% EtOAc in hexanes) to afford 1-bromo-3-(difluoromethoxy)-5-nitrobenzene (160 mg, 0.6 mmol). 1H NMR (400 MHz, CDCl3) δ 6.61 (t, J=71.6 Hz, 1H) 7.65 (s, 1H) 7.96 (s, 1H) 8.21-8.31 (m, 1H).

1. temperatureto cool to room temperature
2. customThe reaction mixture was partitioned between EtOAc and water
3. customthe layers separated
4. extractionthe aqueous portion was extracted (2×25 mL) EtOAc
5. washthe combined organic layers were washed with aqueous 1.0 M NaOH solution (3×25 mL), water (3×25 mL) and brine (50 mL)
6. dry with materialThe organic layer was dried (MgSO4)
7. concentrationconcentrated
8. customThe resulting residue was purified by flash chromatography (SiO2, 0-50% EtOAc in hexanes)

ORD-Eintrag

ord-924cad45cc4e4c358205b612b6332001

Quelldatensatz

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08563553B2