Acetic Acid → Ethyl [3-(2-amino-2-methylpropyl)phenyl]acetate

HRID 1866514Notes

Reaction equation

HRID 1866514 reaction equation
ClCC([NH:5][C:6]([CH3:19])([CH3:18])[CH2:7][C:8]1[CH:9]=[C:10]([CH2:14][C:15]([OH:17])=[O:16])[CH:11]=[CH:12][CH:13]=1)=O.NC(N)=S.[C:24](O)(=O)[CH3:25]>C(O)C>[CH2:24]([O:17][C:15](=[O:16])[CH2:14][C:10]1[CH:11]=[CH:12][CH:13]=[C:8]([CH2:7][C:6]([NH2:5])([CH3:18])[CH3:19])[CH:9]=1)[CH3:25]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 2723790ThioureaHCID 46938812{3-[2-(2-Chloroacetamido)-2-methylpropyl]phenyl}acetic acid

Product 1

HCID 56840061Ethyl [3-(2-amino-2-methylpropyl)phenyl]acetateYield 63%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of {3-[2-(2-chloro-acetylamino)-2-methyl-propyl]-phenyl}-acetic acid (Preparation 48) (5.1 g, 18 mmol), thiourea (1.6 g, 21 mmol) and acetic acid (18 ml) in ethanol (80 ml) was heated to reflux under a nitrogen atmosphere for 16 hours. The reaction mixture was cooled and filtered. The filtrate was reduced in vacuo, the residue dissolved in ethanol (150 ml), saturated with hydrogen chloride gas and the resulting solution heated to reflux for 16 hours. The solvent was reduced in vacuo and the residue partitioned between ethyl acetate (200 ml) and 5% aqueous sodium carbonate (200 ml). The organic extract was washed with saturated sodium chloride (100 ml), dried (sodium sulfate) and reduced in vacuo. The residue was purified by strong cation exchange resin, eluting with methanol and then 2N ammonia in methanol to elute the product. The eluent was concentrated in vacuo giving the title compound as a yellow oil (2.68 g, 63%).

Workup

  1. temperatureto reflux under a nitrogen atmosphere for 16 hours
  2. temperatureThe reaction mixture was cooled
  3. filtrationfiltered
  4. dissolutionthe residue dissolved in ethanol (150 ml), saturated with hydrogen chloride gas
  5. temperaturethe resulting solution heated
  6. temperatureto reflux for 16 hours
  7. customthe residue partitioned between ethyl acetate (200 ml) and 5% aqueous sodium carbonate (200 ml)
  8. extractionThe organic extract
  9. washwas washed with saturated sodium chloride (100 ml)
  10. dry with materialdried (sodium sulfate)
  11. customThe residue was purified by strong cation exchange resin
  12. washeluting with methanol
  13. wash2N ammonia in methanol to elute the product
  14. concentrationThe eluent was concentrated in vacuo

Sources & evidence

ORD record
ord-b6fdb7d5532f4e199a02fc0845305670
Source dataset
uspto-grants-2009_12
Patent number
US07629358B2

Reaction notes

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