Triethylamine → 3-(Benzyloxycarbonyl-ethoxycarbonylmethyl-amino)-propionic acid ethyl ester

HRID 446091Notes

Reaction equation

HRID 446091 reaction equation
Cl.[CH2:2]([O:4][C:5](=[O:8])[CH2:6][NH2:7])[CH3:3].C(N(CC)CC)C.[C:16]([O:20][CH2:21][CH3:22])(=[O:19])[CH:17]=[CH2:18].C(=O)([O-])[O-].[Na+].[Na+].[CH2:29]([O:36][C:37](Cl)=[O:38])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>C(O)C.CC(C)=O>[CH2:29]([O:36][C:37]([N:7]([CH2:18][CH2:17][C:16]([O:20][CH2:21][CH3:22])=[O:19])[CH2:6][C:5]([O:4][CH2:2][CH3:3])=[O:8])=[O:38])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 8821Ethyl AcrylateHCID 10340Sodium CarbonateHCID 10387Benzyl chloroformateHCID 2723640Glycine ethyl ester, hydrochloride

Product 1

HCID 547587953-(Benzyloxycarbonyl-ethoxycarbonylmethyl-amino)-propionic acid ethyl esterYield 92.2%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

To a suspension of glycine ethyl ester hydrochloride (41.9 g, 0.3 mol) in ethanol (300 mL) was added triethylamine (41.8 mL, 0.3 mol) and ethyl acrylate (10.8 mL, 0.1 mol) in an ice bath, and the mixture was stirred at 80° C. for 1 hour. The reaction mixture was concentrated under reduced pressure, and water (400 mL) was added to the residue, and the mixture was extracted with ethyl acetate (200 mL×3). The extract was washed with water (200 mL×2) and saturated aqueous solution of sodium chloride (200 mL) in this order, an the dried with anhydrous sodium sulfate. After the filtration, the filtrate was concentrated under reduced pressure, and the residue was dissolved in acetone (150 mL). To this solution were added aqueous solution of sodium carbonate (11.5 g, 108 mmol) (50 mL) and a solution of benzyloxycarbonyl chloride (18.4 g, 108 mmol) in acetone (50 mL) in an ice bath, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, and water (400 mL) was added to the residue. The mixture was extracted with ethyl acetate (200 mL×3), and the extract was washed with saturated aqueous solution of sodium chloride (200 mL), and dried with anhydrous sodium sulfate. After the filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate, 5:1) to obtain 31.1 g (92%) of the title compound as a colorless oily product.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure, and water (400 mL)
  2. additionwas added to the residue
  3. extractionthe mixture was extracted with ethyl acetate (200 mL×3)
  4. washThe extract was washed with water (200 mL×2) and saturated aqueous solution of sodium chloride (200 mL) in this order
  5. dry with materialan the dried with anhydrous sodium sulfate
  6. filtrationAfter the filtration
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. dissolutionthe residue was dissolved in acetone (150 mL)
  9. concentrationThe reaction mixture was concentrated under reduced pressure, and water (400 mL)
  10. additionwas added to the residue
  11. extractionThe mixture was extracted with ethyl acetate (200 mL×3)
  12. washthe extract was washed with saturated aqueous solution of sodium chloride (200 mL)
  13. dry with materialdried with anhydrous sodium sulfate
  14. filtrationAfter the filtration
  15. concentrationthe filtrate was concentrated under reduced pressure
  16. customthe residue was purified by silica gel column chromatography (hexane:ethyl acetate, 5:1)

Sources & evidence

ORD record
ord-2c7aa61bb141460aa28e3a1ee97e8a00
Source dataset
uspto-grants-2013_07
Patent number
US08476429B2

Reaction notes

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