Hydrochloric Acid → 6-Bromo-2-hydroxy-N-methyl-1-naphthamide

HRID 480451Notes

Reaction equation

HRID 480451 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([C:12](O)=[O:13])=[C:7]([OH:15])[CH:6]=[CH:5]2.CS(Cl)(=O)=O.[CH3:21][NH2:22].Cl>C1COCC1.C1COCC1.CO.[OH-].[Na+].C(N(CC)CC)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([C:12]([NH:22][CH3:21])=[O:13])=[C:7]([OH:15])[CH:6]=[CH:5]2

Participants

9

Reactant 4

HCID 313Hydrochloric Acid2×HCID 6329MethylamineHCID 31297Methanesulfonyl chlorideHCID 187690886-Bromo-2-hydroxynaphthalene-1-carboxylic acid

Product 1

HCID 187690866-Bromo-2-hydroxy-N-methyl-1-naphthamide

Reagents, catalysts & solvents 4

HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 14798Sodium HydroxideSolventHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

To a ice-cooled solution of 6-Bromo-2-hydroxy-1-naphthoic acid (10.0 g) and triethylamine (26.1 mL) in anhydrous THF (300 mL) was added dropwise methanesulfonyl chloride (7.0 mL), and the mixture was stirred for 90 min at room temperature. A solution of methylamine (2M in THF; 60 mL) was added, and the reaction mixture was further stirred for overnight at room temperature. The mixture was acidified with conc. HCl and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over MgSO4 followed by concentrating in vacuo. The residue was washed hexane-ethyl acetate (1:1) to give a light brown powder. The powder was dissolved in THF-MeOH-4N-NaOH (6:1:1, 80 mL), and the mixture was heated at 70° C. for 30 min. After cooling to room temperature, the mixture was acidified with conc. HCl and concentrated in vacuo. The residue was washed with water and AcOEt to give the title compound (4.61 g) as light brown powder.

Workup

  1. stirringthe reaction mixture was further stirred for overnight at room temperature
  2. extractionextracted with ethyl acetate
  3. washThe combined organic layer was washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationby concentrating in vacuo
  6. washThe residue was washed hexane-ethyl acetate (1:1)
  7. customto give a light brown powder
  8. temperaturethe mixture was heated at 70° C. for 30 min
  9. temperatureAfter cooling to room temperature
  10. concentrationconcentrated in vacuo
  11. washThe residue was washed with water and AcOEt

Sources & evidence

ORD record
ord-6864dfbe441749cb8056d3a80e426806
Source dataset
uspto-grants-2003_11
Patent number
US06649643B1

Reaction notes

Loading…