N-bromobutanimide → (6-Bromo-7-methyl-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester

HRID 519221Notes

Reaction equation

HRID 519221 reaction equation
[CH2:1]([O:3][C:4](=[O:19])[CH:5]([N:7]1[C:12]2[CH:13]=[CH:14][C:15]([CH3:17])=[CH:16][C:11]=2[O:10][CH2:9][C:8]1=[O:18])[CH3:6])[CH3:2].[Br:20]N1C(=O)CCC1=O>C(Cl)Cl>[CH2:1]([O:3][C:4](=[O:19])[CH:5]([N:7]1[C:12]2[CH:13]=[C:14]([Br:20])[C:15]([CH3:17])=[CH:16][C:11]=2[O:10][CH2:9][C:8]1=[O:18])[CH3:6])[CH3:2]

Participants

4

Reactant 2

HCID 67184N-bromobutanimideHCID 867276252-(7-Methyl-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester

Product 1

HCID 86727626(6-Bromo-7-methyl-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl esterYield 85%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(7-methyl-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester (21.0 g, 80 mmol) in DCM (250 mL) was added 1-bromopyrrolidine-2,5-dione (15.6 g, 88 mmol) and the reaction mixture was stirred at ambient temperature for 3 h. The reaction mixture was quenched by addition of a saturated solution of thiosulfate in water (50 mL). The organic phase was separated and the aqueous portion was extracted with DCM (3×20 mL). The combined organic phase was washed with brine (100 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 20% EtOAc in petroleum ether) to give -(6-bromo-7-methyl-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester as solid (23.1 g, 85%). LC/MS (Table 1, Method 3) Rt=1.259 min.; MS m/z: 342/344 [M+H]+.

Workup

  1. customThe reaction mixture was quenched by addition of a saturated solution of thiosulfate in water (50 mL)
  2. customThe organic phase was separated
  3. extractionthe aqueous portion was extracted with DCM (3×20 mL)
  4. washThe combined organic phase was washed with brine (100 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography on silica gel (eluting with 20% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-b44caa45bf014147b8203028713034d9
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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