Oxalyl chloride → N-[4-(benzyloxy)benzoyl]glycine tert-butyl ester

HRID 456265Notes

Reaction equation

HRID 456265 reaction equation
C(Cl)(=O)C(Cl)=O.[CH2:7]([O:14][C:15]1[CH:23]=[CH:22][C:18]([C:19]([OH:21])=O)=[CH:17][CH:16]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.Cl.[C:25]([O:29][C:30](=[O:33])[CH2:31][NH2:32])([CH3:28])([CH3:27])[CH3:26].C(N(C(C)C)C(C)C)C>CN(C=O)C.O.ClCCl>[C:25]([O:29][C:30](=[O:33])[CH2:31][NH:32][C:19](=[O:21])[C:18]1[CH:17]=[CH:16][C:15]([O:14][CH2:7][C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)=[CH:23][CH:22]=1)([CH3:28])([CH3:27])[CH3:26]

Participants

9

Reactant 4

HCID 65578Oxalyl chlorideHCID 738804-(Benzyloxy)benzoic acidHCID 81531DiisopropylethylamineHCID 2725036Glycine tert-butyl ester hydrochloride

Product 1

HCID 66811832N-[4-(benzyloxy)benzoyl]glycine tert-butyl ester

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

Oxalyl chloride (8.7 mL, 99.7 mmol) and several drops of N,N-dimethylformaldehyde (hereinafter DMF) were added to a solution of dichloromethane (40 mL) containing 4-benzyloxybenzoic acid (11.1 g, 48.6 mmol) under ice-cooling. The mixture was stirred at room temperature for 2 hours, and then the solvent was evaporated. The resulting residue was dissolved in dichloromethane (100 mL), and then glycine tert-butyl ester hydrochloride (8.20 g, 48.9 mmol) and N-ethyl-N,N-diisopropylamine (21 mL, 120 mmol) were added thereto under ice-cooling. The mixture was stirred at room temperature for 19 hours, and then water was added thereto to terminate the reaction. The mixture was extracted with dichloromethane twice, and the organic layers were combined and concentrated. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate, 9:1 to 2:1, v/v) to give N-[4-(benzyloxy)benzoyl]glycine tert-butyl ester. All the given ester was dissolved in methanol (165 mL), and 20% palladium hydroxide-carbon (926 mg) was added thereto. The mixture was vigorously stirred under a hydrogen atmosphere at room temperature for 3.5 hours. The reaction mixture was filtered through Celite and then concentrated to give 12.2 g of the title compound (colorless crystalline solid, yield: quantitative).

Workup

  1. temperaturecooling
  2. customthe solvent was evaporated
  3. dissolutionThe resulting residue was dissolved in dichloromethane (100 mL)
  4. temperatureunder ice-cooling
  5. stirringThe mixture was stirred at room temperature for 19 hours
  6. customto terminate
  7. customthe reaction
  8. extractionThe mixture was extracted with dichloromethane twice
  9. concentrationconcentrated
  10. customThe resulting residue was purified by silica gel column chromatography (hexane

Sources & evidence

ORD record
ord-d3b4404cf0f04cf8b8f2b8e31f7bc146
Source dataset
uspto-grants-2013_07
Patent number
US08497397B2

Reaction notes

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