Reaction #42470

Reaction equation

Methyl 3-bromo-5-(butylamino)-4-methoxybenzoate

BBr3

→

title compound

Yield 88.5%

Methyl 3-bromo-5-(butylamino)-4-hydroxybenzoate

Yield 88.5%

Solvents

methylene chloride

Conditions

Workup

1. 1
   ConcentrationThe mixture was concentrated under reduced pressure
2. 2
   workup.DISSOLUTIONthe residue was dissolved in methylene chloride
3. 3
   workup.ADDITIONsaturated sodium bicarbonate was added
4. 4
   workup.ADDITIONmethanol was added dropwise
5. 5
   workup.STIRRINGAfter stirring for 30 min
6. 6
   workup.STIRRINGthe mixture was stirred at room temperature for 1 h
7. 7
   OtherThe solvent was removed
8. 8
   workup.DISSOLUTIONthe residue dissolved in methylene chloride
9. 9
   Washwashed with water, saturated sodium bicarbonate (15 mL), and brine
10. 10
    Dryingdried (magnesium sulfate)
11. 11
    Filtrationfiltered
12. 12
    Concentrationconcentrated under reduced pressure
13. 13
    OtherPurification by flash column chromatography (silica, 1:20, ethyl acetate/hexanes)

Procedure

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.

Source