Benzenepropanoic acid → N-(3-phenylpropionyl)-L-proline benzyl ester

HRID 1720506Notes

Reaction equation

HRID 1720506 reaction equation
Cl.[CH2:2]([O:9][C:10](=[O:16])[C@@H:11]1[CH2:15][CH2:14][CH2:13][NH:12]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(N(CC)CC)C.[C:24]1([CH2:30][CH2:31][C:32](O)=[O:33])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C1CCC(N=C=NC2CCCCC2)CC1>C(Cl)Cl>[CH2:2]([O:9][C:10](=[O:16])[C@@H:11]1[CH2:15][CH2:14][CH2:13][N:12]1[C:32](=[O:33])[CH2:31][CH2:30][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Participants

6

Reactant 4

HCID 107Benzenepropanoic acidHCID 8471TriethylamineHCID 10868DicyclohexylcarbodiimideHCID 2733413Proline benzyl ester hydrochloride

Product 1

HCID 45139423N-(3-phenylpropionyl)-L-proline benzyl esterYield 93.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of L-proline benzyl ester hydrochloride (20.0 g) in methylene chloride (250 ml) were added triethylamine (11.5 ml), 3-phenylpropionic acid (13.7 g) and DCC (18.8 g) under ice-cooling, and the mixture was stirred for 2 hours. After stirring at room temperature for 14 hours, the insoluble material was filtered off, and the filtrate was concentrated. The residue was dissolved in ethyl acetate, and the solution was washed with 1N hydrochloric acid, saturated aqueous solution of sodium bicarbonate and saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography (eluate: hexane-ethyl acetate). To thus-obtained N-(3-phenylpropionyl)-L-proline benzyl ester (26.1 g) in 1% water-containing methanol (200 ml) was added 10% Pd--C (3.0 g), and the mixture was stirred at room temperature under hydrogen atmosphere for 2.5 hours. The catalyst was filtered off, and the filtrate was concentrated to give 17.4 g of the title compound.

Workup

  1. temperaturecooling
  2. stirringAfter stirring at room temperature for 14 hours
  3. filtrationthe insoluble material was filtered off
  4. concentrationthe filtrate was concentrated
  5. dissolutionThe residue was dissolved in ethyl acetate
  6. washthe solution was washed with 1N hydrochloric acid, saturated aqueous solution of sodium bicarbonate and saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel column chromatography (eluate: hexane-ethyl acetate)

Sources & evidence

ORD record
ord-9036e7c8033c48ff811aedeed9fb48eb
Source dataset
uspto-grants-1996_04
Patent number
US05506256

Reaction notes

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