Ethyl bromoacetate → N-(5-acetyl-2-methylphenyl)iminodiacetic acid diethyl ester

HRID 1893536Notes

Reaction equation

HRID 1893536 reaction equation
[CH3:1][C:2]1[CH:8]=[CH:7][C:6]([C:9]2([CH3:14])[O:13]CCO2)=[CH:5][C:3]=1[NH2:4].Br[CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18].C(N([CH2:29][CH3:30])C(C)C)(C)C>C(OCC)(=O)C.CCCCCC>[CH2:20]([O:19][C:17](=[O:18])[CH2:16][N:4]([CH2:16][C:17]([O:19][CH2:29][CH3:30])=[O:18])[C:3]1[CH:5]=[C:6]([C:9](=[O:13])[CH3:14])[CH:7]=[CH:8][C:2]=1[CH3:1])[CH3:21]

Participants

5

Reactant 3

HCID 7748Ethyl bromoacetateHCID 81531DiisopropylethylamineHCID 668820662-Methyl-5-(2-methyl-1,3-dioxolan-2-yl)aniline

Product 1

HCID 66880575N-(5-acetyl-2-methylphenyl)iminodiacetic acid diethyl esterYield 99.3%

Reagents, catalysts & solvents 1

HCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
140 °C

Procedure

The compound (9.87 g, 51.08 mmol) obtained in step A, ethyl bromoacetate (23 ml, 207 mmol) and N,N-diisopropylethylamine (45 ml, 265 mmol) were mixed, and the mixture was stirred with heating at 140° C. for 200 min. The reaction mixture was cooled, diluted with an ethyl acetate-hexane=1:1 mixed solvent, and the organic layer was washed with 10% aqueous citric acid solution, saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over anhydrous magnesium sulfate. The insoluble material was filtered off, and the solution was concentrated under reduced pressure. The obtained oil was dissolved in tetrahydrofuran (160 ml), 6N aqueous hydrochloric acid solution (25 ml) was added, and the mixture was stirred at room temperature for 30 min. To the reaction mixture were added water and an ethyl acetate-hexane=1:1 mixed solvent, and the organic layer was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over anhydrous magnesium sulfate. The insoluble material was filtered off, and the solution was concentrated under reduced pressure. The obtained oil was purified by silica gel column chromatography (ethyl acetate-hexane) to give the title compound (16.30 g, yield 99%) as a yellow oil.

Workup

  1. temperatureThe reaction mixture was cooled
  2. washthe organic layer was washed with 10% aqueous citric acid solution, saturated aqueous sodium hydrogen carbonate and saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationThe insoluble material was filtered off
  5. concentrationthe solution was concentrated under reduced pressure
  6. dissolutionThe obtained oil was dissolved in tetrahydrofuran (160 ml)
  7. addition6N aqueous hydrochloric acid solution (25 ml) was added
  8. stirringthe mixture was stirred at room temperature for 30 min
  9. additionTo the reaction mixture were added water
  10. washan ethyl acetate-hexane=1:1 mixed solvent, and the organic layer was washed with saturated aqueous sodium hydrogen carbonate and saturated brine
  11. dry with materialdried over anhydrous magnesium sulfate
  12. filtrationThe insoluble material was filtered off
  13. concentrationthe solution was concentrated under reduced pressure
  14. customThe obtained oil was purified by silica gel column chromatography (ethyl acetate-hexane)

Sources & evidence

ORD record
ord-fc4a4ff3a09f442085522ea65d7b8367
Source dataset
uspto-grants-2013_08
Patent number
US08513235B2

Reaction notes

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