Reaction #2007

Reaction equation

benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate

D-Homophenylalanine benzyl ester

triethylamine

N-(t-butoxycarbonyl)-α-methylalanine

→

(R)-α-[(2-t-Butoxycarbonylamino-2-methyl-1-oxopropyl)amino]benzenebutanoic acid benzyl ester

Solvents

methylene chloride

methylene chloride

Conditions

Workup

1. 1
   workup.STIRRINGThe reaction mixture was stirred at room temperature for 2.5 h
2. 2
   Otherthen quenched
3. 3
   workup.ADDITIONby adding saturated brine (25 ml)
4. 4
   ExtractionThe two phase system was extracted with methylene chloride (3×25 ml)
5. 5
   Dryingthe combined methylene chloride extracts dried over magnesium sulfate powder
6. 6
   Filtrationfiltered
7. 7
   Otherevaporated on a rotary evaporator under reduced pressure
8. 8
   Otherto give a colorless oil that
9. 9
   Otheron standing at room temperature
10. 10
    Otherchromatographed on silica gel using an eluant
11. 11
    OtherThe product was isolated
12. 12
    Otherafter evaporation of the volatiles as a white solid

Procedure

D-Homophenylalanine benzyl ester (0.87 g; 3.23 mmol), triethylamine (900 ml) and N-(t-butoxycarbonyl)-α-methylalanine (656 mg; 3.23 mmol) were dissolved in dry methylene chloride (6.5 ml) and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP-reagent) (1.43 g; 3.23 mmol) was added with stirring in small batches over 10 minutes. The reaction mixture was stirred at room temperature for 2.5 h then quenched by adding saturated brine (25 ml). The two phase system was extracted with methylene chloride (3×25 ml) and the combined methylene chloride extracts dried over magnesium sulfate powder, filtered and evaporated on a rotary evaporator under reduced pressure to give a colorless oil that solidified to an off white solid on standing at room temperature. This solid material was taken up in the minimum volume of methylene chloride and chromatographed on silica gel using an eluant composed of ethyl acetate and hexanes in the ratio 1:3 v/v. The product was isolated after evaporation of the volatiles as a white solid. The yield of the desired product was 1.30 g (88.5%). FAB-MS: -calculated for C26H34N2O5 454.2; found 455.5 (M+1).

Source