The general procedure for the synthesis of 3,5-dibromoanisole from methanol and 1,3-dibromo-5-nitrobenzene was as follows: 1,3-dibromo-5-nitrobenzene (21.07 g, 75 mmol), freshly powdered potassium hydroxide (7.57 g, 135 mmol) and tetrabutyl ammonium bromide (2.42 g, 7.5 mmol) were suspended in tetramethylurea (80 mL). A solution of methanol (4.81 g, 6.09 mL, 150 mmol) dissolved in 20 mL of tetramethylurea was added slowly and dropwise to the above brown suspension over a period of 15 min at room temperature. The reaction mixture was stirred continuously for 24 h at room temperature before it was quenched by pouring it into ice (150 g) and extracted with tert-butyl methyl ether (3 x 250 mL). The organic phases were combined, dried with magnesium sulfate and subsequently concentrated under reduced pressure to give the crude product. The crude product was purified by reduced pressure distillation (124 °C, 10 Torr) to give 16.74 g (84% yield) of 3,5-dibromoanisole as a light yellow solid.
