Sodium Bicarbonate → 4-(2,6-Dibromo-4-nitrophenoxy)-2-isopropylanisole

Temperature

0 °C

A 22 L jacketed vessel equipped with mechanical stirring and a nitrogen inlet adapter was charged with dimethylformamide (4 L) and 3-isopropyl-4-methoxyphenol (462.8 g, 2.59 moles). The solution was cooled to 0° C., and KHMDS (5.50 L of 0.5M toluene solution, 2.25 moles) was added over 1.5 h while maintaining the temperature of the mixture below 2° C. The reaction mixture was stirred for 30 min at 2° C., then 1,3-dibromo-2-iodo-5-nitro-benzene (798.6 g, 1.96 moles) was added in portions, still maintaining temperature of the mixture below 2° C. After the addition was complete, the reaction mixture was allowed to stir at room temperature for 2 h or until the reaction was complete as assayed by HPLC. The reaction mixture was cooled once more to 2° C. and ethyl acetate (4.5 L) was added, followed by slow addition of saturated aqueous sodium bicarbonate (6 L) while maintaining the temperature of the reaction mixture below 28° C. The organic layer was washed with saturated aqueous sodium chloride solution, then concentrated by rotary evaporation. The black, oily residue was taken up in acetone (3.87 L). Water (0.77 L) was added to the solution over 30 min with heating to 42° C. The solution was seeded with crystals of the product, cooled to 0° C., and stirred for 15 min. The resulting crystals of 4-(2,6-dibromo-4-nitrophenoxy)-2-isopropylanisole (665 g, 76.1%) were recovered by filtration and dried for 48 h by evaporation under air flow at room temperature.

1. customequipped
2. temperaturewhile maintaining the temperature of the mixture below 2° C
3. stirringThe reaction mixture was stirred for 30 min at 2° C.
4. temperaturestill maintaining temperature of the mixture below 2° C
5. additionAfter the addition
6. stirringto stir at room temperature for 2 h or until the reaction
7. temperatureThe reaction mixture was cooled once more to 2° C.
8. temperaturewhile maintaining the temperature of the reaction mixture below 28° C
9. washThe organic layer was washed with saturated aqueous sodium chloride solution
10. concentrationconcentrated by rotary evaporation
11. additionWater (0.77 L) was added to the solution over 30 min
12. temperaturewith heating to 42° C
13. temperaturecooled to 0° C.
14. stirringstirred for 15 min
15. filtrationThe resulting crystals of 4-(2,6-dibromo-4-nitrophenoxy)-2-isopropylanisole (665 g, 76.1%) were recovered by filtration
16. customdried for 48 h by evaporation under air flow at room temperature

ORD record

ord-104c6c83b0484abfac2695bbc35a1560

Source dataset

uspto-grants-2004_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06806381B2