Diisopropylethylamine → methyl 5-bromo-1-(2,6-dichlorophenyl)-2-oxo-1,4-dihydro-2H-3,1-benzoxazine-7-carboxylate

HRID 394215Notes

Reaction equation

HRID 394215 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10](Br)[C:11]=1[CH2:12][O:13][C:14]([NH:16][C:17]1[C:22]([Cl:23])=[CH:21][CH:20]=[CH:19][C:18]=1[Cl:24])=[O:15])[C:5]([O:7][CH3:8])=[O:6].C(N(C(C)C)CC)(C)C>CN(C=O)C.[Cu]I>[Br:1][C:2]1[C:11]2[CH2:12][O:13][C:14](=[O:15])[N:16]([C:17]3[C:22]([Cl:23])=[CH:21][CH:20]=[CH:19][C:18]=3[Cl:24])[C:10]=2[CH:9]=[C:4]([C:5]([O:7][CH3:8])=[O:6])[CH:3]=1

Participants

5

Reactant 2

HCID 81531DiisopropylethylamineHCID 22648016Methyl 3,5-dibromo-4-[({[(2,6-dichlorophenyl)amino]carbonyl}oxy)methyl]benzoate

Product 1

HCID 22647893methyl 5-bromo-1-(2,6-dichlorophenyl)-2-oxo-1,4-dihydro-2H-3,1-benzoxazine-7-carboxylate

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of methyl 3,5-dibromo-4-[({[(2,6-dichlorophenyl)amino]carbonyl}oxy)methyl]benzoate (1 g, 1.96 mmol, 1 eq) in DMF (20 mL) was added CuI (411 mg, 2.16 mmol, 1.1 eq) and diisopropylethylamine (0.51 mL, 2.95 mmol, 1.5 eq). Degassed the reaction flask with argon and placed in a 140° C. oil bath. After 2.5 h the reaction was cooled. The mixture was filtered to remove inorganics. The solvent was removed under reduced pressure. The residue was dissolved in CH2Cl2, and washed with water. The aqueous layer was back-extracted 2× with CH2Cl2. The organic extracts were combined, dried over anhydrous Na2SO4, filtered and concentrated. The residue was triturated with Et2O leaving 283 mg of solid methyl 5-bromo-1-(2,6-dichlorophenyl)-2-oxo-1,4-dihydro-2H-3,1-benzoxazine-7-carboxylate. The supernatant was further purified by flash column chromatography on silica gel eluting with 2:1 CH2Cl2/hexanes giving an additional 309 mg of not quite pure product. Mass spectrum (ESI) 430.0 (M+1); 432.0 (M+3), 434.0 (M+5).

Workup

  1. customDegassed the reaction flask with argon
  2. customplaced in a 140° C.
  3. temperatureAfter 2.5 h the reaction was cooled
  4. filtrationThe mixture was filtered
  5. customto remove inorganics
  6. customThe solvent was removed under reduced pressure
  7. dissolutionThe residue was dissolved in CH2Cl2
  8. washwashed with water
  9. extractionThe aqueous layer was back-extracted 2× with CH2Cl2
  10. dry with materialdried over anhydrous Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe residue was triturated with Et2O leaving 283 mg of solid methyl 5-bromo-1-(2,6-dichlorophenyl)-2-oxo-1,4-dihydro-2H-3,1-benzoxazine-7-carboxylate
  14. customThe supernatant was further purified by flash column chromatography on silica gel eluting with 2:1 CH2Cl2/hexanes giving an additional 309 mg of not quite pure product

Sources & evidence

ORD record
ord-3c8d4c0eb2fd4acdac5cebd586795e82
Source dataset
uspto-grants-2004_10
Patent number
US06809199B2

Reaction notes

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