Reaction #1904081

Reaction equation

1-(2-amino-5-bromo-phenyl)-ethanone

glycine ethyl ester hydrogen chloride

→

7-bromo-5-methyl-1,3-dihydro-benzo[e][1,4]diazepin-2-one

Yield 16.1%

Solvents

pyridine

Conditions

Workup

1. 1
   Temperaturewas heated
2. 2
   Temperatureat reflux for 24 hrs under nitrogen
3. 3
   TemperatureThe reaction mixture was cooled
4. 4
   Othersolvent removed
5. 5
   workup.ADDITIONresidue was treated with a saturated aqueous ammonium chloride solution (200 mL)
6. 6
   workup.ADDITIONEthyl acetate (300 mL) was added
7. 7
   Otherorganic layer was separated
8. 8
   Dryingdried (MgSO4)
9. 9
   Concentrationconcentrated
10. 10
    Otherthe residue purified on silica gel column (hexane:ethyl acetate/1:1)

Procedure

A mixture of 1-(2-amino-5-bromo-phenyl)-ethanone (8 g, 37 mmol) and glycine ethyl ester hydrogen chloride (6.7 g, 48 mmol) in pyridine was heated at reflux for 24 hrs under nitrogen. The reaction mixture was cooled, solvent removed, and residue was treated with a saturated aqueous ammonium chloride solution (200 mL). Ethyl acetate (300 mL) was added and organic layer was separated, dried (MgSO4), concentrated, and the residue purified on silica gel column (hexane:ethyl acetate/1:1) to give 7-bromo-5-methyl-1,3-dihydro-benzo[e][1,4]diazepin-2-one as a brown solid (1.51 g, 16%). 1H NMR (DMSO-d6): δ 10.49 (s, 1H), 7.92 (d, J=2.0 Hz, 1H), 7.66 (dd, J=8.7, 2.1 Hz, 1H), 7.08 (d, J=8.7 Hz, 1H), 3.91 (s, 2H), 2.39 (s, 3H). MS (ESI) m/z 253/255 ([M+H]+); Anal. calcd for C10H9BrN2O: C, 47.46; H, 3.58; N, 11.07. Found: C, 47.58; H, 3.52; N, 10.95.

Source