Benzoyl Peroxide → 5-(n-Tert-butoxycarbonyl-n-methylamino-methyl)-2-nitrobenzoic acid methyl ester

HRID 557451Notes

Reaction equation

HRID 557451 reaction equation
[CH3:1][O:2][C:3](=[O:14])[C:4]1[CH:9]=[C:8]([CH3:10])[CH:7]=[CH:6][C:5]=1[N+:11]([O-:13])=[O:12].Br[N:16]1C(=O)CC[C:17]1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.[C:41]([O:45][C:46]([O:48]C(OC(C)(C)C)=O)=O)([CH3:44])([CH3:43])[CH3:42]>C(#N)C.C(N(CC)CC)C.C1C=CC=CC=1>[CH3:1][O:2][C:3](=[O:14])[C:4]1[CH:9]=[C:8]([CH2:10][N:16]([C:46]([O:45][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:48])[CH3:17])[CH:7]=[CH:6][C:5]=1[N+:11]([O-:13])=[O:12]

Participants

8

Reactant 4

HCID 7187Benzoyl PeroxideHCID 67184N-bromobutanimideHCID 90495Di-tert-butyl dicarbonateHCID 3314122Methyl 5-methyl-2-nitrobenzoate

Product 1

HCID 580183275-(n-Tert-butoxycarbonyl-n-methylamino-methyl)-2-nitrobenzoic acid methyl ester

Reagents, catalysts & solvents 3

HCID 241BenzeneSolventHCID 6342AcetonitrileSolventHCID 8471TriethylamineSolvent

Procedure

To 1.0 g of the crude product of 5-methyl-2-nitrobenzoic acid methyl ester synthesized in the foregoing step 1, there were added 1.4 g of N-bromosuccinimide, 0.5 g of benzoyl peroxide and 30 mL of benzene, the resulting mixture was refluxed with stirring for 4 hours and the solvent was distilled off under reduced pressure. The resulting residue was dissolved in 30 mL of acetonitrile, this solution was added to 36 mL of a 2M methylamine solution in THF and the mixture was further stirred at room temperature for 10 minutes. The solvent was distilled off under reduced pressure, then ethyl acetate was added, followed by the washing thereof four times with a 1M hydrochloric acid solution. The resulting ethyl acetate phase was washed with a saturated sodium hydrogen carbonate aqueous solution and a saturated common salt solution and the solvent was distilled off under reduced pressure. The crude product thus prepared was dissolved in 30 mL of acetonitrile, 1.1 g of di-tert-butyl-dicarbonate and 1.1 mL of triethylamine were added to the solution and the resulting mixture was stirred at room temperature overnight. The solvent was distilled off under reduced pressure, ethyl acetate was added thereto, the insoluble matter was then removed through filtration and the filtrate thus obtained was concentrated under reduced pressure. The resulting crude product was purified by the silica gel chromatography (hexane:ethyl acetate=90:10→80:20) to thus give 0.71 g of the title compound. MS (ESI+): m/z 325 (MH+).

Workup

  1. temperaturethe resulting mixture was refluxed
  2. distillationthe solvent was distilled off under reduced pressure
  3. dissolutionThe resulting residue was dissolved in 30 mL of acetonitrile
  4. additionthis solution was added to 36 mL of a 2M methylamine solution in THF
  5. stirringthe mixture was further stirred at room temperature for 10 minutes
  6. distillationThe solvent was distilled off under reduced pressure
  7. additionethyl acetate was added
  8. washThe resulting ethyl acetate phase was washed with a saturated sodium hydrogen carbonate aqueous solution
  9. distillationa saturated common salt solution and the solvent was distilled off under reduced pressure
  10. customThe crude product thus prepared
  11. stirringthe resulting mixture was stirred at room temperature overnight
  12. distillationThe solvent was distilled off under reduced pressure, ethyl acetate
  13. additionwas added
  14. customthe insoluble matter was then removed through filtration
  15. customthe filtrate thus obtained
  16. concentrationwas concentrated under reduced pressure
  17. customThe resulting crude product was purified by the silica gel chromatography (hexane:ethyl acetate=90:10→80:20) to thus give 0.71 g of the title compound

Sources & evidence

ORD record
ord-741a8e46e3e140ed88e16ac68f089e75
Source dataset
uspto-grants-2011_11
Patent number
US08058432B2

Reaction notes

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