1,1'-Carbonyldiimidazole → 6-bromo-4-ethyl-4-methyl-1,4-dihydro-2H-3,1-benzoxazin-2-one

HRID 915900Notes

Reaction equation

HRID 915900 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][C:3]=1[C:9](=[O:11])[CH3:10].[CH2:12]([Mg]Br)[CH3:13].[C:16](N1C=CN=C1)(N1C=CN=C1)=[O:17]>C1COCC1>[Br:8][C:5]1[CH:6]=[CH:7][C:2]2[NH:1][C:16](=[O:17])[O:11][C:9]([CH2:12][CH3:13])([CH3:10])[C:3]=2[CH:4]=1

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 110747461-(2-Amino-5-bromophenyl)ethan-1-oneHCID 178418443HCID 178418443, compound

Product 1

HCID 112656926-bromo-4-ethyl-4-methyl-1,4-dihydro-2H-3,1-benzoxazin-2-oneYield 46.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 1-(2-amino-5-bromophenyl)-ethanone (10.00 g, 46.70 mmol) in THF (150 mL) was added 3.0M ethyl magnesium bromide (50 mL, 150 mmol) slowly at 0° C. over 20 minutes. The reaction was stirred 1 hr at 0° C., quenched with ammonium chloride solution (sat.) and extracted with ethyl acetate several times. The organic layer was washed with brine and dried over magnesium sulfate. The concentrated crude material was dissolved in THF (150 mL). 1,1′-Carbonyldiimidazole (9.00 g, 56.04 mmol) was added and the reaction was stirred overnight at room temperature. The reaction was partitioned between ammonium chloride solution (sat.) and ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated. Flash silica gel column separation with 30% ethyl acetate/hexane followed by trituration with ether gave 6-bromo-4-ethyl-4-methyl-1,4-dihydro-2H-3,1-benzoxazin-2-one as a white solid (5.84 g, 46%). 1H NMR (DMSO-d6): δ 10.28 (s, 1H), 7.43 (m, 2H), 6.783 (d, J=8.3 Hz, 1H), 2.02 (m, 1H), 1.87 (m, 1H), 1.57 (s, 3H), 0.82 (t, J=7.3 Hz, 3H). MS (ESI) m/z 270/272 ([M+H]+); MS (ESI) m/z 268/270 ([M−H]−); HRMS: calcd for C11H12BrNO2, 269.0051; found (ESI_FT), 270.01259. Anal. Calcd for C11H12BrNO2: C, 48.91; H, 4.48; N, 5.19. Found: C, 48.94; H, 4.38; N, 5.00.

Workup

  1. customquenched with ammonium chloride solution (sat.)
  2. extractionextracted with ethyl acetate several times
  3. washThe organic layer was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationThe concentrated crude material
  6. dissolutionwas dissolved in THF (150 mL)
  7. stirringthe reaction was stirred overnight at room temperature
  8. customThe reaction was partitioned between ammonium chloride solution (sat.) and ethyl acetate
  9. dry with materialThe organic layer was dried over magnesium sulfate
  10. concentrationconcentrated
  11. customFlash silica gel column separation with 30% ethyl acetate/hexane

Sources & evidence

ORD record
ord-da2047bf08c74289a154c6f237b141bf
Source dataset
uspto-grants-2007_09
Patent number
US07268149B2

Reaction notes

Loading…