Dichloromethane → N-Methylpiperidine

Participants

Reaction Steps

A suspension of 1.500 g (4.68 mmoles) of Z-(L)-Pro-(L)-AlaOH (Sigma) in 70 ml of dry methylene chloride (CH2Cl2) was brought in an 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. Adding 0.650 g (4.81 mmoles) of anhydrous 1-hydroxybenzotriazole (HOBT), the temperature was kept, under stirring, at approximately -15° C. for a further 20 minutes, then adding 0.780 g (4.53 mmoles) of CytH (Aldrich). Leaving the temperature of the system free to rise to room temperature, after approximately one hour another 0.580 ml (4.77 mmoles) of NMP were added. The mixture was left under stirring, static argon, out of the light, for 12 hours. The solid white precipitate was filtered away and washed with a little methylene chloride, which was put back into the reaction solution of a yellowish colour. This was extracted in succession using 5% NaHCO3 (3×30 ml); saturated aqueous NaCl (2×30 ml); 4% KHSC4 (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, obtaining a residual yellowish oil which was taken up with anhydrous ethyl ether. The ether solution thus obtained was brought back to a dry state under vacuum and the residual yellow oil, taken up with the smallest possible volume of acetate mixture of ethyl/n-hexane (2:1) was purified by flash-chromatography in a normal phase (SiO2, eluant ethyl acetate/n-hexane: 2/1.5). Having joined and concentrated the fractions of interest under vacuum a dense pale yellow oil was left which, when taken up with a minimum quantity of methanol, was precipitated in an excess of water, obtaining an abundant flocculent whiteish precipitate. After two hours rest in a cold chamber the off-white precipitate was filtered and dried under vacuum on P2O5 for 24 hours. 1.520 g (70.7%) of an analytically pure, slightly rubbery off-white solid were recovered.

Provenance & Evidence