(S)-1-(tert-Butoxycarbonyl)-4,4-dimethylpyrrolidine-2-carboxylic acid

Uses

(S)-1-(tert-Butoxycarbonyl)-4,4-dimethylpyrrolidine-2-carboxylic acid is a cyclic amino acid derivative that is used in the synthesis of peptides and peptidomimetics. It contains a pyrrolidine ring and a carboxylic acid group at position 2. This compound is an optical isomer, and its (S)-stereoisomer is the most commonly used in scientific experiments, such as synthesizing tert-butyl (S)-2-(hydroxymethyl)-4,4-dimethylpyrrolidine-1-carboxylate, (S)-4,4-dimethylpyrrolidine-2-carboxylic acid, and so on.

Synthesis

To a solution of 1-(tert-butyl) 2-methyl (S)-4,4-dimethylpyrrolidine-1,2-dicarboxylate (4.85 g, 18.86 mmol) in THF (40 mL) was dropwise added lithium hydroxide monohydrate aqueous solution (1.5 g, 20 mL)  at 0 °C. At the end of the addition, the mixture was stirred at rt for 2.0 h. After that, the THF solvent was removed and 50 mL of water was added to the mixture. The resulting mixture was washed with EtOAc (30 mL x 3). The aqueous phase was adjusted to pH=1 with hydrochloric acid (1 M) and extracted with EtOAc (50 mL x 3). The combined organic layers were washed with brine, dried over anhydrous Na2S04, and concentrated in vacuo to give (S)-1-(tert-Butoxycarbonyl)-4,4-dimethylpyrrolidine-2-carboxylic acid as a white solid (4.35 g, 95%).