Azide → (S)-2-((tert-Butoxycarbonyl)amino)-3-(5-(diethoxyphosphoryl)-1H-1,2,3-triazol-1-yl)propanoic acid

Participants

Reaction Steps

Boc-azidoalanine benzyl ester 11 (360 mg, 1.13 mmol) and diethyl ethynylphosphonate 9 (370 mg, 2.26 mmol) were dissolved in dry toluene (4 mL) in a round bottom flask and degassed by free-pump-thaw (3 cycles). In a separate round bottom flask equipped with a magnetic stir bar, Cp*Ru(COD)Cl wherein COD is η4-cyclooctadiene (65 mg, 0.15 mmol) and Cp* is η5-C5Me5 was dissolved in degassed toluene (3 mL) under argon atmosphere. To this, the solution of the azide and alkyne was added dropwise via a cannula over 1 min The resultant solution was stirred at room temperature under argon for 1.5 h while being monitored by TLC. The reaction mixture was directly loaded to a pad of silica gel (10 cm×3 cm diameter, packed with 10% ethyl acetate/hexane) and eluted with 60% ethyl acetate/hexane to remove the ruthenium catalyst. The cycloaddition product was not further purified but used directly in the subsequent deprotection step because the product and the unreacted alkyne have very similar mobility on silica gel (Rf=0.3, 50% ethyl acetate/hexane, a brown spot stained with p-anisaldehyde).

Provenance & Evidence