Bromine → 2,3,5-Tribromo-4-methoxy-aniline

HRID 712187Notes

Reaction equation

HRID 712187 reaction equation
[Br:1][C:2]1[C:8]([Br:9])=[C:7]([O:10][CH3:11])[C:6]([Br:12])=[C:5](Br)[C:3]=1[NH2:4].BrC1C=C(C=C(Br)C=1OC)N.BrBr>C(Cl)Cl>[Br:1][C:2]1[C:8]([Br:9])=[C:7]([O:10][CH3:11])[C:6]([Br:12])=[CH:5][C:3]=1[NH2:4]

Participants

5

Reactant 3

HCID 24408BromineHCID 133995503,5-Dibromo-4-methoxyanilineHCID 133995532,3,5,6-Tetrabromo-4-methoxybenzenamine

Product 1

HCID 133995512,3,5-Tribromo-4-methoxy-aniline

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

3,5-Dibromo-4-methoxy-aniline (13.04 g, 46.42 mmol) was dissolved in DCM (500 mL) and a solution of bromine (2.38 mL, 46.42 mmol) in DCM (80 mL) was added dropwise. A thick, beige precipitate formed. After 45 minutes, the mixture was quenched with NaHCO3 solution (saturated, aq) to pH 9, the layers separated and the aqueous layer extracted into DCM (3×50 mL). The combined organic phase was washed with brine, dried over Na2SO4 and concentrated to dryness under reduced pressure to give a brown solid. The mixture was purified by chromatography, Biotage SP4, 2×120 g Si cartridges in series, 10-50% EtOAc in cyclohexane. The relevant fractions were combined to give 2,3,5-tribromo-4-methoxy-aniline which was contaminated with some 2,3,5,6-tetrabromo-4-methoxy-aniline (12.64 g). The column was eluted further to give recovered starting material 3,5-dibromo-4-methoxy-aniline (2.84 g). The recovered starting material, 3,5-dibromo-4-methoxy-aniline (2.84 g, 10.11 mmol) was dissolved in DCM (100 mL) and a solution of bromine (0.52 mL, 10.11 mmol) in DCM (5 mL) was added dropwise. The mixture was stirred at rt for 2.5 h. The mixture was quenched with NaHCO3 solution (saturated, aq) to pH 9, the layers separated and the aqueous layer extracted into DCM (3×50 mL). The combined organic phase was dried over Na2SO4 and concentrated to dryness under reduced pressure. This material was combined with the impure 2,3,5-tribromo-4-methoxy-aniline and purified by chromatography, Biotage SP4, 330 g Si cartridge, 10% EtOAc in cyclohexane. The relevant fractions were combined to give the desired compound as an orange oil, 9.95 g (60%). m/z: 357.93/359.89/361.90/363.84 [M+H]+.

Workup

  1. washThe column was eluted further
  2. customto give
  3. customrecovered
  4. customThe mixture was quenched with NaHCO3 solution (saturated, aq) to pH 9
  5. customthe layers separated
  6. extractionthe aqueous layer extracted into DCM (3×50 mL)
  7. dry with materialThe combined organic phase was dried over Na2SO4
  8. concentrationconcentrated to dryness under reduced pressure
  9. custompurified by chromatography, Biotage SP4, 330 g Si cartridge, 10% EtOAc in cyclohexane

Sources & evidence

ORD record
ord-8b1d9042ba66441aa8fa397a05b9a4d0
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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