Methanol → (S)-1-Benzyl 2-methyl pyrrolidine-1,2-dicarboxylate

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Reaction Steps

A dry 1-L, one-necked, round-bottomed flask was equipped with a Liebig condenser fitted with a rubber septum and a magnetic stirrer. The condenser was temporarily removed, and the flask was charged with 33.7 g (0.135 mol) of N-benzyloxycarbonyl-(S)-proline and 400 mL of anhydrous methanol (Mallinckrodt). The flask was flushed with nitrogen through the septum. The mixture was stirred, and 24.6 mL (28.4 g, 0.2 mol) of boron trifluoride etherate was added via cannula. The resulting mixture was stirred and refluxed for 1 hr under nitrogen. After the solvent was removed under reduced pressure, the residue was vigorously stirred with 200 mL of ice-water. The mixture was extracted with ethyl acetate (3×100 mL). The extacts were combined and successively washed with brine (2×20 mL), a 1M aqueous sodium hydrogen carbonate solution (3×20 mL), and brine (2×20 mL), and dried over anhydrous sodium sulfate. After the removal of the solvent under reduced pressure, a colorless oil was obtained. The oil was dissolved in 100 mL of dry toluene (distilled over CaH2), and the solvent was removed under reduced pressure to remove water from the oil. This treatment was repeated to give 35.9 g of N-benzyloxycarbonyl-(S)-proline methyl ester is a colorless oil (containing a small amount of toluene), [α]D21 -53.9° (methanol, c 1.0).

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