Chlorotrimethylsilane → trans-1-(4-nitrobenzyloxycarbonyl)-4-trimethylsilyloxy-L-proline

Participants

Reaction Steps

608 μl of chlorotrimethylsilane and 670 μl of triethylamine, whilst ice-cooling, were added to a solution of 620 mg of trans-4-hydroxy-1-(4-nitrobenzyloxycarbonyl)-L-proline in 20 ml of dry acetonitrile, and the resulting mixture was stirred at room temperature for 1 hour. At the end of this time, the solvent was removed by distillation under reduced pressure, and the resulting residue was mixed with an aqueous solution of sodium chloride. The mixture was then extracted with ethyl acetate. The extract was washed with an aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate. The solvent was then removed by distillation under reduced pressure, to give 648 mg of trans-1-(4-nitrobenzyloxycarbonyl)-4-trimethylsilyloxy-L-proline as a powder. The whole of this was dissolved in 14 ml of dry acetonitrile, and then 330 mg of N,N'-carbonyldiimidazole were added. The mixture thus obtained was stirred at room temperature for 1 hour. At the end of this time, a solution of 630 mg of 1-[2-(4-nitrobenzyloxycarbonyl)oxyethyl]piperazine in 2 ml of dry acetonitrile was added to the reaction mixture, and the resulting mixture was stirred overnight an room temperature and then at 40° C. for a further 1 hour. The reaction mixture was then mixed with 14 ml of 1N aqueous hydrochloric acid and stirred at room temperature for 1 hour. At the end of this time, the mixture was concentrated by evaporation under reduced pressure, and the concentrate was made slightly alkaline by the addition of an aqueous solution of sodium hydrogencarbonate; it was then extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure, and the resulting residue was purified by column chromatography through silica gel, using a 9:1 by volume mixture of ethyl acetate and methanol as the eluent, to give 589 mg of the title compound, as a powder. The infrared absorption spectrum and nuclear magnetic resonance spectrum of the compound thus obtained were identical with those of the compound prepared as described in step 90(b)(i) above.

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