Acetic Acid → 5-Azido-3-methyl-3,5-dihydro-4H-benzo[d][1,2]diazepin-4-one

To a well stirred solution of 4,5-dihydro-3-methyl-3H-2,3-benzodiazepin-4-one (3.0 g, 17.2 mmol) in anhydrous tetrahydrofuran (100 mL) at −78° C. was added a solution of 0.5 M potassium bis(trimethylsilyl)amide in toluene (45 mL, 22.4 mmol). The reaction mixture was stirred for another 15 min followed by addition of a pre-cooled solution of 2,4,6-triisopropylbenzenesulfonyl azide (trisyl azide) (5.8 g, 19 mmol) in THF (0.4M) via a cannula over a period of 2 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 (4.9 mL, 86 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-4,5-dihydro-3-methyl-3H-2,3-benzodiazepin-4-one was purified by flash chromatography (silica) using 10% EtOAc in hexane. The azide was obtained in 75% yield.

1. waitAfter 5 min
2. stirringstirring
3. waitcontinued for another 6 h
4. washwashed with water (300 mL), aqueous NaHCO3 (2×150 mL), 0.5 N HCl (200 mL) and brine (150 mL)
5. customThe solvent was removed
6. customthe 5(R,S)-azido-4,5-dihydro-3-methyl-3H-2,3-benzodiazepin-4-one was purified by flash chromatography (silica)

ORD record

ord-f0e70b34fba44743aacf478f5e67a560

Source dataset

uspto-grants-2002_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06432944B1