Methanol → 2-Methyl 1-(phenylmethyl) (2S,4R)-4-hydroxy-1,2-pyrrolidinedicarboxylate

Beteiligte Stoffe

Reaktionsschritte

To methanol (500 ml) was added conc. sulfuric acid (10 ml) below 30° C. To this solution was added (2S,4R)-1-benzyloxycarbonyl-2-carboxy-4-hydroxypyrrolidine (100 g) and the resulting mixture was heated under reflux for 4 hours. To the mixture was added triethylamine (63 ml) below 10° C. and the mixture was evaporated in vacuo keeping a bath temperature of rotary evaporator below 40° C. to give a syrup. To this syrup were added tetrahydrofuran (100 ml) and toluene (200 ml) successively, and then evaporated in vacuo keeping the bath temperature below 40° C. This procedure was performed once more to give (2S,4R)-1-benzyloxycarbonyl-4-hydroxy-2-methoxycarbonylpyrrolidine. The compound obtained above was dissolved in a mixture of ethyl acetate (1000 ml) and triethylamine (63 ml). To this solution was added dropwise a solution of methanesulfonyl chloride (35 ml) in ethyl acetate (100 ml) at 0°-5° C. over a period of 1.5 hours. This mixture was stirred at the same temprature for additional 30 minutes. This mixture was poured into ice-cold water (1000 ml) with stirring. The organic layer was separated, and washed with 1N hydrochloric acid (1000 ml), saturated aqueous sodium hydrogen carbonate (1000 ml) and brine (1000 ml) successively. This organic layer was evaporated in vacuo keeping the bath temperature below 40° C. to give (2S,4R)-1-benzyloxycarbonyl-4-methanesulfonyloxy-2-methoxycarbonylpyrrolidine. The compound obtained above was dissolved in a of tetrahydrofuran (200 ml) and ethanol (300 ml). To this solution was added sodium borohydride(28.5 g) by three portions below 10° C. and then this mixture was stirred at 25°-30° C. for 2 hours. This mixture was poured into ice-cold water (5000 ml) containing conc. sulfuric acid (92 ml) with vigorous stirring, and the stirring was continued for additional 1 hour to give a white crystal. This crystal was collected by filtration and washed with ice-cold water (500 ml) to give (2S,4R)-1-benzyloxycarbonyl-2-hydroxymethyl-4-methanesulfonyloxypyrrolidine (95.2 g).

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