Sodium Thiosulfate → 2-[2-oxo4-(1H-tetrazol-1-yl)-1-pyrrolidinyl]butanamide

Participants

Reaction Steps

In a 0.25 L three necked flask under argon with magnetic stirring, a degassed solution of 2S4-pyrol-pyrrolidin-2-one 223 as a single enantiomer (1.18 g, 0.0049 mol.) in THF (35 ml) is cooled to −78° C. and N-Bromosuccinimide (0.877 g, 0.005 mol.) is added by portions. The reaction mixture is stirred for 0.5 h, and the Na2S2O3 (0.9 g) is added to quench the NBS. The reaction mixture is warmed to room temperature, concentrated in vacuo and purified by chromatography on silicagel (EtOH/CH2Cl2: 05/95 (v/v)) to afford, after recrystallisation in MeCN, (2S)-2-[4-(2-bromo-1H-pyrrol-1-yl)-2-oxo-1-pyrrolidinyl]butanamide 234 (1.05 g, 67%) as a white solid. Alternatively, using the same experimental procedure and 2 equiv. of N-Bromo-succinimide, dibromopyrrole 237 can be obtained. 5.8. Synthesis of Tetrazolyl Derivatives Alternatively to § 5.6, reaction of 2-[4-amino-2-oxo-1-pyrrolidinyl]butanamide with triethyl orthoformiate, NaN3 and AcOH provided 2-[2-oxo4-(1H-tetrazol-1-yl)-1-pyrrolidinyl]butanamide 67. 5.9. Synthesis of (4H-1,2,4-triazol-4-yl) Derivatives Alternatively to § 5.6, reaction of 2-[4-amino-2-oxo-1-pyrrolidinyl]butanamides with pyridine and 1,2-bis((dimethylamino)methylene)hydrazine provided 2-[2-oxo-4-(4H-1,2,4-triazol-4-yl)-1-pyrrolidinyl]butanamides 65 and 66.

Provenance & Evidence