Boron tribromide → Methyl 3-bromo-5-(butylamino)-4-hydroxybenzoate

Temperature

0 °C

To a −78° C. solution of the Methyl 3-bromo-5-(butylamino)-4-methoxybenzoate (520 mg) in methylene chloride (10 mL) was added BBr3 (8 ml of 1.0 M solution in methylene chloride) dropwise and the reaction mixture was stirred for 18 h. The mixture was concentrated under reduced pressure, and the residue was dissolved in methylene chloride and saturated sodium bicarbonate was added. The mixture was cooled to 0° C. and methanol was added dropwise. After stirring for 30 min, the mixture was stirred at room temperature for 1 h. The solvent was removed, and the residue dissolved in methylene chloride, washed with water, saturated sodium bicarbonate (15 mL), and brine, dried (magnesium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 1:20, ethyl acetate/hexanes) provided 440 mg of the title compound: 1H NMR (300 MHz, CDCl3) δ 7.52, 7.19, 3.88, 3.18, 1.65, 1.46, 0.97.

1. concentrationThe mixture was concentrated under reduced pressure
2. dissolutionthe residue was dissolved in methylene chloride
3. additionsaturated sodium bicarbonate was added
4. additionmethanol was added dropwise
5. stirringAfter stirring for 30 min
6. stirringthe mixture was stirred at room temperature for 1 h
7. customThe solvent was removed
8. dissolutionthe residue dissolved in methylene chloride
9. washwashed with water, saturated sodium bicarbonate (15 mL), and brine
10. dry with materialdried (magnesium sulfate)
11. filtrationfiltered
12. concentrationconcentrated under reduced pressure
13. customPurification by flash column chromatography (silica, 1:20, ethyl acetate/hexanes)

ORD record

ord-f4bc502469014f0b90c11cc5ae3c4a48

Source dataset

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07727997B2