Methyl iodide → (2S,4S)-4-methoxypyrrolidine-2-carboxylic acid

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Reaction Steps

A stirred solution of (2S,4S)-1-(benzyloxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid (35.9 g, 135.4 mmol) in dry THF (870 mL) is treated under nitrogen with sodium hydride (11.78 g, 491 mmol) and methyl iodide (38.5 g, 271 mmol), using a procedure similar to that published in J. Med. Chem. 1988, 31, 875, except that reflux is carried out for 16 h. The crude extracted product of this alkylation reaction, (2S,4S)-1-(benzyloxycarbonyl)-4-methoxypyrrolidine-2-carboxylic acid, is then dissolved in methanol (200 mL), treated with 6.2 g of 20% palladium hydroxide on carbon, and stirred at room temperature overnight under 1 atmosphere of hydrogen. The reaction mixture is filtered, washed with methanol, and evaporated in vacuo. The resulting solid is suspended in dichloromethane (450 mL) and filtered to give 11.5 g (91%) of the pure title compound: MS: 146 (M+H)+; 500 MHz 1H NMR (d6-DMSO) δ

Provenance & Evidence