反应详情

A suspension of 1.500 g (4.68 mmoles) of Z-(L)-Pro-(L)-AlaOH (Sigma) in 60 ml of dry methylene chloride (CH2Cl2) was brought under argon atmosphere to a temperature of approximately -20° C. On stabilization of the temperature, the following were added under stirring in quick succession: 0.620 ml (4.74 mmoles) of isobutylchloroformate (IBCF) and 0.580 ml (4.77 mmoles) of N-methylpiperidine (NMP), leaving the system under stirring for approximately 2 minutes. A solution precooled to -15° C. for 30 minutes of 0.880 g (4.47 mmoles) of TrpH.HCl and 0.550 ml (4.52 mmoles) of NMP in 15 ml of anhydrous N,N-dimethylformamide (DMF) was then added to the white suspension. Under stirring, the temperature of the system was allowed to rise to room temperature. After approximately 3.5 hours of reaction, the white precipitate was filtered away and washed with a little CH2Cl2. The latter was put back into the reaction solution of a yellowish colour, which was extracted in succession using 5% NaHCO3 (3×30 ml); saturated aqueous NaCl (2×30 ml); 4% KHSO4 (3×30 ml) and finally saturated aqueous NaCl (3×30 ml), discarding the aqueous phases. The organic phase extracted was left in a cool chamber under argon and on anhydrous Na2SO4 for 24 hours. The desiccant was then filtered away and the solution concentrated to a small volume under vacuum. The residual yellowish liquid was dripped under stirring into 150 ml of petroleum ether (30/50), obtaining a rubbery grey precipitation. The solution was decanted and the residual mass was taken up with a minimum of CH2Cl2 and further purified by flash-chromatography in a normal phase (SiO2, eluant CH2Cl2 /n-Hexane/n-PrOH 10:1.5:0.5). Having collected and joined together the fractions of interest, most of the eluant was eliminated under vacuum and precipitation with an excess of n-Hexane takes place. There was a large amount of whiteish precipitate, slightly rubbery, which was filtered after a couple of hours and dried on P2O5 under vacuum for 24 hours. 1.300 g (62.8%) of an analytically pure whiteish solid were recovered.

1. customwas brought under argon atmosphere to a temperature of approximately -20° C
2. additionOn stabilization of the temperature, the following were added