Acetic Acid → HCID 131723426, compound

Participants

Reaction Steps

To a well stirred solution of 2,3,4,5-tetrahydro-3-methyl-4-oxo-1H-2,3-benzodiazepine-2-carboxylic acid, 1,1-dimethylethyl ester (1.0 g, 3.62 mmol) in anhydrous tetrahydrofuran (30 mL) at −78° C. was added a solution of 0.5 M potassium bis(trimethylsilyl)amide in toluene (9.0 mL, 4.5 mmol). The reaction mixture was stirred for another 15 min followed by addition of a pre-cooled solution (−78° C.) of 2,4,6-triisopropylbenzenesulfonyl azide (trisyl azide) (1.23 g, 4.0 mmol) in THF (0.4M) via a cannula over a period of 1 min (Evans, et al., J. Amer. Chem. Soc., 1990, 112, 4011-4030; Butcher, et al., Tetrahedron Lett., 1996, 37 (37), 6685-6688). After 5 min, acetic acid (1.0 mL, 18 mmol) was added and stirring continued for another 6 h. The reaction mixture was diluted with EtOAc (300 mL), washed with water (300 mL), aqueous NaHCO3 (2×150 mL), 0.5 N HCl (200 mL) and brine (150 mL). The solvent was removed and the 5(R,S)-azido-2,3,4,5-tetrahydro-3-methyl-4-oxo-1H-2,3-benzodiazepine-2-carboxylic acid, 1,1-dimethylethyl ester was purified by flash chromatography (silica) using 10% EtOAc in hexane. The azide was obtained in 60% yield.

Provenance & Evidence