Reaction #865

Reaction equation

N-benzyloxycarbonyl-β-benzyl-L-aspartyl-D-isoleucine

(S)-α-ethylbenzylamine

water

HOBt

→

N-benzyloxycarbonyl-β-benzyl-L-aspartyl-D-isoleucine (S)-α-ethylbenzylamide

Yield 33.1%

Solvents

methylene chloride

Conditions

Workup

1. 1
   Temperatureunder cooling
2. 2
   Temperatureunder cooling
3. 3
   Otherovernight
4. 4
   Otherat room temperature
5. 5
   ConcentrationThe reaction mixture was concentrated under reduced pressure, and 150 ml of ethyl acetate
6. 6
   workup.ADDITIONwas added
7. 7
   WashThe resulting residue was washed two times each with 70 ml of aqueous 5% citric acid
8. 8
   DryingThe resulting organic layer was dried with anhydrous magnesium sulfate
9. 9
   Otherthe magnesium sulfate was removed by filtration
10. 10
    Concentrationthe resulting filtrate was concentrated under reduced pressure
11. 11
    workup.DISSOLUTIONThe resulting residue was dissolved in chloroform
12. 12
    Concentrationconcentrated under reduced pressure
13. 13
    WashThe resulting solid residue was washed with ethyl acetate
14. 14
    Otherdried

Procedure

To a solution of 6.69 g (14.2 mmols) of N-benzyloxycarbonyl-β-benzyl-L-aspartyl-D-isoleucine and 2.04 g (15.1 mmols) of (S)-α-ethylbenzylamine in 200 ml of methylene chloride were added 2.73 g (14.2 mmols) of water-soluble carbodiimide hydrochloride and 1.92 g (14.2 mmols) of HOBt under cooling and stirred for one hour under cooling and then overnight at room temperature. The reaction mixture was concentrated under reduced pressure, and 150 ml of ethyl acetate was added. The resulting residue was washed two times each with 70 ml of aqueous 5% citric acid, once with 70 ml of water, two times each with 70 ml of aqueous 5% sodium hydrogencarbonate and once with 70 ml of brine in that order. The resulting organic layer was dried with anhydrous magnesium sulfate, the magnesium sulfate was removed by filtration, and the resulting filtrate was concentrated under reduced pressure. The resulting residue was dissolved in chloroform and concentrated under reduced pressure. The resulting solid residue was washed with ethyl acetate and dried to obtain 2.81 g (4.7 mmols) of N-benzyloxycarbonyl-β-benzyl-L-aspartyl-D-isoleucine (S)-α-ethylbenzylamide.

Source