N-bromobutanimide → Methyl 2,3,4,5-tetrahydro-7-bromo-4-methyl-3-oxo-1H-1,4-benzodiazepine-2-acetate

HRID 1976264Notes

Reaction equation

[CH3:1][N:2]1[CH2:8][C:7]2[CH:9]=[CH:10][CH:11]=[CH:12][C:6]=2[NH:5][CH:4]([CH2:13][C:14]([O:16][CH3:17])=[O:15])[C:3]1=[O:18].[Br:19]N1C(=O)CCC1=O>C(Cl)Cl>[Br:19][C:10]1[CH:11]=[CH:12][C:6]2[NH:5][CH:4]([CH2:13][C:14]([O:16][CH3:17])=[O:15])[C:3](=[O:18])[N:2]([CH3:1])[CH2:8][C:7]=2[CH:9]=1

Participants

Conditions

Temperature: 28 °C

Procedure

Methyl 2,3,4,5-tetrahydro-4-methyl-3-oxo-1H-1,4-benzodiazepine-2-acetate (100 g, 0.4 mole) and n-Bu4 N Br (13 g, 0.04 mole) were added to CH2Cl2 (1.0 liter) and refluxed for 0.5 hr. The reaction mixture was cooled to 28° C. and N-Bromosuccinimide added in small portions (72.8 g, 0.41 mole). The reaction was stirred at ambient temperature for 1.0 hr then washed with 5% NaHCO3 solution (400 ml) then water (2×400 ml) CH2Cl2 (800 ml) was replaced with hexane (800 ml) via ‘put and take’ distillation, the resulting slurry was cooled, filtered and washed with hexane. The product was dried in vacuo to yield the title compound (123 g, 93%). HPLC analysis showed 0.7% residual starting material and 0.7% 7,9-dibromide.

Workup

temperaturerefluxed for 0.5 hr
washthen washed with 5% NaHCO3 solution (400 ml)
distillationdistillation
temperaturethe resulting slurry was cooled
filtrationfiltered
washwashed with hexane
customThe product was dried in vacuo

Sources & evidence

ORD record: ord-46b139e2410f42f3b70b7f864bbf9d25
Source dataset: uspto-grants-2001_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06225465B1

Reaction notes

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