Isopropylamine → HCID 43510674, compound

HRID 869218Notes

Reaction equation

HRID 869218 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:8]([N+:11]([O-])=O)=[CH:7][C:3]=1[C:4]([OH:6])=O.S(Cl)(Cl)=O.[CH:18]([NH2:21])([CH3:20])[CH3:19].[Cl-].[NH4+]>[Zn].O.CO.C(N(CC)CC)C.C1COCC1>[NH2:11][C:8]1[CH:9]=[CH:10][C:2]([F:1])=[C:3]([CH:7]=1)[C:4]([NH:21][CH:18]([CH3:20])[CH3:19])=[O:6]

Participants

10

Reactant 4

HCID 6363IsopropylamineHCID 24386Thionyl ChlorideHCID 25517Ammonium ChlorideHCID 2809972-Fluoro-5-nitrobenzoic acid

Product 1

HCID 43510674HCID 43510674, compound

Reagents, catalysts & solvents 5

HCID 23994ZincCatalystHCID 887MethanolSolventHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

A mixture of 2-fluoro-5-nitrobenzoic acid (600 mg) and thionyl chloride (2 mL) was heated under reflux for 15 hours. The reaction liquid was concentrated under reduced pressure, followed by an azeotropic process with toluene to give a yellow crystal. To a mixture of the yellow crystal and THF (11 mL), triethylamine (0.47 mL) and isopropylamine (0.29 mL) were added under ice cooling and stirred at room temperature for 5 hours. The reaction liquid was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and then dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to give a yellow crystal. To a mixture of the yellow crystal (723 mg) and methanol (8 mL) and water (3 mL), ammonium chloride (2.05 g) and zinc powder (2.09 g) were added, and the mixture was heated under reflux for 3 hours. After filtration of the reaction suspension through celite, the filtrate was concentrated under reduced pressure. The residue was poured into saturated aqueous sodium hydrogen carbonate and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and then dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent; chloroform:methanol) to give 5-amino-2-fluoro-N-isopropylbenzamide (527 mg) as a light brown crystal.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 15 hours
  3. customThe reaction liquid
  4. concentrationwas concentrated under reduced pressure
  5. customto give a yellow crystal
  6. additionwere added under ice cooling
  7. customThe reaction liquid
  8. extractionextracted with ethyl acetate
  9. washThe organic layer was washed with saturated aqueous sodium chloride
  10. dry with materialdried over anhydrous sodium sulfate
  11. distillationthe solvent was distilled off under reduced pressure
  12. customto give a yellow crystal
  13. additionwere added
  14. temperaturethe mixture was heated
  15. temperatureunder reflux for 3 hours
  16. filtrationAfter filtration of the reaction suspension through celite
  17. concentrationthe filtrate was concentrated under reduced pressure
  18. additionThe residue was poured into saturated aqueous sodium hydrogen carbonate
  19. extractionextracted with ethyl acetate
  20. washThe organic layer was washed with saturated aqueous sodium chloride
  21. dry with materialdried over anhydrous sodium sulfate
  22. distillationthe solvent was distilled off under reduced pressure
  23. customThe residue was purified by silica gel column chromatography (eluent; chloroform:methanol)

Sources & evidence

ORD record
ord-56b59cff8a094532996b704dacf2992b
Source dataset
uspto-grants-2015_03
Patent number
US08969336B2

Reaction notes

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