1,1'-Carbonyldiimidazole → Brofoxine

HRID 413110Notes

Reaction equation

HRID 413110 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][C:3]=1[C:9]([OH:12])([CH3:11])[CH3:10].[C:13](N1C=CN=C1)(N1C=CN=C1)=[O:14]>C1COCC1>[Br:8][C:5]1[CH:6]=[CH:7][C:2]2[NH:1][C:13](=[O:14])[O:12][C:9]([CH3:10])([CH3:11])[C:3]=2[CH:4]=1

Participants

4

Reactant 2

HCID 682631,1'-CarbonyldiimidazoleHCID 120422752-(2-Amino-5-bromophenyl)propan-2-ol

Product 1

HCID 30630Brofoxine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 2-(2-amino-5-bromophenyl)propan-2-ol (18 g, 78 mmol) in dry THF (150 mL) was added 1,1′-carbonyldiimidazole (15.5 g, 94 mmol) under nitrogen. The reaction solution was heated at 50° C. overnight. The solvent was removed in vacuo and the residue was dissolved in ethyl acetate (100 mL). The solution was washed with 1N aqueous hydrochloride solution (2×40 mL), brine (20 mL), and dried with MgSO4. After removal of solvent in vacuo, 6-bromo-4,4-dimethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one was obtained as a white solid (20 g, 100%): mp 199-200° C.; 1H-NMR (DMSO-d6) δ10.32 (s, 1H, D2O exchangeable), 7.48 (d, 1H, J=2.1 Hz), 7.43 (dd, 1H, J=8.5, 2.1 Hz), 6.84 (d, 1H, J=8.4 Hz), 161 (s, 6H).

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionthe residue was dissolved in ethyl acetate (100 mL)
  3. washThe solution was washed with 1N aqueous hydrochloride solution (2×40 mL), brine (20 mL)
  4. dry with materialdried with MgSO4
  5. customAfter removal of solvent in vacuo

Sources & evidence

ORD record
ord-aa041aa2121e466e8088e676f5815cbe
Source dataset
uspto-grants-2003_05
Patent number
US06566358B2

Reaction notes

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