Di-tert-butyl dicarbonate → 3,6-Diaza-bicyclo(3.2.0)heptane-6-carboxylic acid tert-butyl ester

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Reaction Steps

3-tert-Butoxycarbonylamino-4-hydroxymethyl-pyrrolidine-1-carboxylic acid benzyl ester. To a 3 L round-bottomed flask, was added the filtered reaction mixture of 3-amino-4-hydroxymethyl-pyrrolidine-1-carboxylic acid benzyl ester in pentanol/ethanol mixture. To the mixture sodium bicarbonate (30.8 g, 367 mmol), H2O (655 mL), and Boc anhydride (38 g, 174.1 mmol) were added. The mixture was stirred under N2(g) for 15 h at room temperature. The biphasic mixture was then separated and the organics were washed with brine (655 mL). The organics were dried with magnesium sulfate, filtered, and concentrated under reduced pressure. The material was warmed to 98° C. in toluene/heptanes (280 mL each) and then filtered. The filtrate was slowly cooled to room temperature and stirred for 20 h. The resulting solids were filtered and washed with heptanes to provide the title compound (39.5 g, 64% over two steps). 1H-NMR (CD3OD, 400 MHz): 7.31 (m, 5H), 5.11 (s, 2H), 4.20 (m, 1H), 3.50-3.70 (m, 4H), 3.34-3.42 (m, 1H), 3.18-3.29 (m, 1H), 2.49 (m, 1H), 1.44 (s, 9H).

Provenance & Evidence