Bromine → 5-Bromo-4-chloro-2-hydroxybenzoic acid

Temperature

-70 °C

Methanol (2.1 liters) was added to 4-chlorosalicylic acid (60 g) and sodium acetate (120 g), and the mixture was cooled to -70° C. and stirred. To this mixture was added dropwise a solution of bromine (55.7 g) in methanol (557 ml) over 1.5 hours. After the reaction mixture was allowed to warm to room temperature, the solvent was distilled off under reduced pressure. The residue was acidified by addition of dilute hydrochloric acid (2 liters). The precipitate was filtered off, dissolved in ethyl acetate, dried over anhydrous magnesium sulfate, and the solvent was concentrated. The deposited crystals were recrystallized from hydrous ethanol to obtain 5-bromo-4-chlorosalicylic acid (43.8 g, mp. 208°-213° C.). According to the same manner as that described in Reference Example 1, by using this compound as the starting compound, 6-bromo-7-chloro-2,2-dimethyl-2H-1,3-benzoxazin-4-one (29.2 g) (Compound A-26) was obtained. The physical properties are shown in Table 1.

1. temperatureto warm to room temperature
2. distillationthe solvent was distilled off under reduced pressure
3. additionThe residue was acidified by addition of dilute hydrochloric acid (2 liters)
4. filtrationThe precipitate was filtered off
5. dissolutiondissolved in ethyl acetate
6. dry with materialdried over anhydrous magnesium sulfate
7. concentrationthe solvent was concentrated
8. customThe deposited crystals were recrystallized from hydrous ethanol

ORD record

ord-f43bcb43dd8842c6a8b413685b204e1d

Source dataset

uspto-grants-1993_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05270308