4-(Benzyloxy)benzoic acid → N-[4-(benzyloxy)benzoyl]glycine methyl ester

HRID 1099570Notes

Reaction equation

HRID 1099570 reaction equation
O1C=CN=C1Cl.[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.[CH3:25][O:26][C:27](=[O:30])[CH2:28][NH2:29].C(N(C(C)C)C(C)C)C>CN(C=O)C.O.ClCCl>[CH3:25][O:26][C:27](=[O:30])[CH2:28][NH:29][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

Participants

8

Reactant 4

HCID 738804-(Benzyloxy)benzoic acidHCID 81531DiisopropylethylamineHCID 122755Glycine methyl ester hydrochlorideHCID 133710742-Chloro-1,3-oxazole

Product 1

HCID 27681983N-[4-(benzyloxy)benzoyl]glycine methyl ester

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

Oxazolyl chloride (4.0 mL, 45.9 mmol) and several drops of DMF were added to a solution of dichloromethane (5 mL) containing 4-benzyloxybenzoic acid (2.29 g, 10.0 mmol) under ice-cooling, and then dichloromethane (2.5 mL) was further added thereto. The mixture was stirred at room temperature for 2.5 hours, and the solvent was evaporated. The resulting residue was dissolved in dichloromethane (20 mL), and glycine methyl ester hydrochloride (1.39 g, 11.1 mmol) and N-ethyl-N,N-diisopropylamine (4.4 mL, 25.2 mmol) were added thereto under ice-cooling. The mixture was stirred at room temperature for 18 hours, and then water was added thereto to terminate the reaction. The mixture was extracted with dichloromethane, and the organic layers were combined and concentrated. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate, 3:4 to 0:1, v/v) to give N-[4-(benzyloxy)benzoyl]glycine methyl ester. Then, 1.66 g of this ester was dissolved in a solvent mixture of methanol (8 mL) and THF (8 mL). To the resulting mixture, 20% palladium hydroxide-carbon (168 mg) was added. The mixture was vigorously stirred at room temperature under a hydrogen atmosphere for 4 hours. The reaction mixture was filtered through Celite and then concentrated to give 1.19 g of the title compound (white powder, yield: 85%).

Workup

  1. temperaturecooling
  2. customthe solvent was evaporated
  3. dissolutionThe resulting residue was dissolved in dichloromethane (20 mL)
  4. temperatureunder ice-cooling
  5. stirringThe mixture was stirred at room temperature for 18 hours
  6. customto terminate
  7. customthe reaction
  8. extractionThe mixture was extracted with dichloromethane
  9. concentrationconcentrated
  10. customThe resulting residue was purified by silica gel column chromatography (hexane

Sources & evidence

ORD record
ord-2f78448c711445948d141363dbf57e68
Source dataset
uspto-grants-2012_03
Patent number
US08143446B2

Reaction notes

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