Benzoyl Peroxide → N-(2,4-dimethoxy-benzyl),N-(2-ethoxycarbonyl-5-hydroxy-benzyl)glycine ethyl ester

HRID 2077250Notes

Reaction equation

HRID 2077250 reaction equation
[CH2:1]([O:3][C:4](=[O:20])[C:5]1[CH:10]=[CH:9][C:8]([O:11][Si](C(C)(C)C)(C)C)=[CH:7][C:6]=1[CH3:19])[CH3:2].BrN1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.[CH2:47]([O:49][C:50](=[O:64])[CH2:51][NH:52][CH2:53][C:54]1[CH:59]=[CH:58][C:57]([O:60][CH3:61])=[CH:56][C:55]=1[O:62][CH3:63])[CH3:48].C(=O)([O-])[O-].[K+].[K+]>C(Cl)(Cl)(Cl)Cl.CN(C=O)C>[CH2:47]([O:49][C:50](=[O:64])[CH2:51][N:52]([CH2:53][C:54]1[CH:59]=[CH:58][C:57]([O:60][CH3:61])=[CH:56][C:55]=1[O:62][CH3:63])[CH2:19][C:6]1[CH:7]=[C:8]([OH:11])[CH:9]=[CH:10][C:5]=1[C:4]([O:3][CH2:1][CH3:2])=[O:20])[CH3:48]

Participants

8

Reactant 5

HCID 7187Benzoyl PeroxideHCID 11430Potassium CarbonateHCID 67184N-bromobutanimideHCID 19895532Ethyl 2-(2,4-dimethoxybenzylamino)acetateHCID 671102614-(tert-Butyl-dimethyl-silanyloxy)-2-methyl-benzoic acid ethyl ester

Product 1

HCID 67110496N-(2,4-dimethoxy-benzyl),N-(2-ethoxycarbonyl-5-hydroxy-benzyl)glycine ethyl esterYield 43%

Reagents, catalysts & solvents 2

HCID 5943Carbon TetrachlorideSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 20 g (68 mmol) of 4-(tert-butyl-dimethyl-silanyloxy)-2-methyl-benzoic acid ethyl ester, 12.1 g (68 mmol) of N-bromosuccinimide, 1.5 g (6.8 mmol) of benzoyl peroxide in 230 mL of carbon tetrachloride was heated at reflux temperature for 5 hours. The resultant mixture was cooled, filtered through a plug of silica gel, and concentrated under reduced pressure. To the residue (12.2 g) was added 8.0 g (28.7 mmol) of N-(2,4-dimethoxy-benzyl)glycine ethyl ester, 3.96 g (28.7 mmol) of potassium carbonate, and 65 mL of anhydrous DMF and the mixture was stirred for 6.5 hours. The mixture was then partitioned into a biphasic water-ethyl acetate mixture and the isolated organic layer was washed with brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by flash chromatography: eluting the desired product from silica gel with a gradient of 10-90% ethyl acetate in hexanes. 5.33 g of the title compound (yellow oil) was isolated; MS (ESI+): 432.2 (M+1)

Workup

  1. temperaturewas heated
  2. temperatureat reflux temperature for 5 hours
  3. filtrationfiltered through a plug of silica gel
  4. concentrationconcentrated under reduced pressure
  5. customThe mixture was then partitioned into a biphasic water-ethyl acetate mixture
  6. washthe isolated organic layer was washed with brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated
  9. customThe residue was purified by flash chromatography
  10. washeluting the desired product from silica gel with a gradient of 10-90% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-c6c92681a3c24b5ba6ada668594510de
Source dataset
uspto-grants-2011_04
Patent number
US07928120B2

Reaction notes

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