Chlorosuccinimide → Methyl 3-amino-4-chloro-2-((3-hydroxypropyl)amino]benzoate

HRID 1398836Notes

Reaction equation

HRID 1398836 reaction equation
[Cl:1]N1C(=O)CCC1=O.[NH2:9][C:10]1[C:11]([NH:20][CH2:21][CH2:22][CH2:23][OH:24])=[C:12]([CH:17]=[CH:18][CH:19]=1)[C:13]([O:15][CH3:16])=[O:14]>C(#N)C.C(=O)([O-])O.[Na+]>[NH2:9][C:10]1[C:11]([NH:20][CH2:21][CH2:22][CH2:23][OH:24])=[C:12]([CH:17]=[CH:18][C:19]=1[Cl:1])[C:13]([O:15][CH3:16])=[O:14]

Participants

5

Reactant 2

HCID 31398Chlorosuccinimide2×HCID 68736607Methyl 3-amino-2-[(3-hydroxypropyl)amino]benzoate

Product 1

HCID 68739849Methyl 3-amino-4-chloro-2-((3-hydroxypropyl)amino]benzoateYield 16.4%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 516892Sodium BicarbonateSolvent

Procedure

N-Chlorosuccinimide (74.1 g, 555 mmol) was added to a stirred solution of methyl 3-amino-2-[(3-hydroxypropyl)amino]benzoate (81.9 g, 370 mmol) in acetonitrile (1480 mL) at room temperature, and the mixture was stirred at room temperature for 16 hr. Additional N-chlorosuccinimide (9.88 g, 74.0 mmol) was added to the mixture, and the mixture was stirred at room temperature for 90 min. The mixture was diluted with saturated aqueous sodium hydrogen carbonate, concentrated in vacuo, and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with a 20-45% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the title compound as a brown oil (15.7 g, 60.8 mmol, 16%).

Workup

  1. stirringthe mixture was stirred at room temperature for 90 min
  2. concentrationconcentrated in vacuo
  3. extractionextracted with ethyl acetate
  4. washThe combined organic layer was washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash column chromatography on silica gel eluting with a 20-45% ethyl acetate/n-hexane gradient mixture
  9. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-141b767aa9a543f7a43b126c7479c019
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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