Hydrochloric Acid → 2-[6-(bromomethyl)-7-chloro-2-oxo-4-phenyl-2H-chromen-3-yl]acetic acid

HRID 488866Notes

Reaction equation

HRID 488866 reaction equation
C([O:3][C:4](=[O:25])[CH2:5][C:6]1[C:7](=[O:24])[O:8][C:9]2[C:14]([C:15]=1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[CH:13][C:12]([CH3:22])=[C:11]([Cl:23])[CH:10]=2)C.[Br:26]N1C(=O)CCC1=O.Cl>C(OCC)(=O)C.C(O)(=O)C>[Br:26][CH2:22][C:12]1[CH:13]=[C:14]2[C:9](=[CH:10][C:11]=1[Cl:23])[O:8][C:7](=[O:24])[C:6]([CH2:5][C:4]([OH:3])=[O:25])=[C:15]2[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 67184N-bromobutanimideHCID 22267257ethyl(7-chloro-6-methyl-2-oxo-4-phenyl-2H-chromen-3-yl)acetate

Product 1

HCID 222672172-[6-(bromomethyl)-7-chloro-2-oxo-4-phenyl-2H-chromen-3-yl]acetic acid

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of ethyl(7-chloro-6-methyl-2-oxo-4-phenyl-2H-chromen-3-yl)acetate (3.5 g) in ethyl acetate (50 ml) was combined with N-bromosuccinimide (2.1 g) and 2,2′-azoisobutyronitrile (48.3 mg), and heated under reflux for 1 hour. After cooling, the reaction solution was washed with water followed by a saturated aqueous solution of sodium hydrogen carbonate and a saturated aqueous solution of sodium chloride. After drying over magnesium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by a silica gel column chromatography (eluent: ethyl acetate-hexane=1:4) to obtain the crude crystal (approximately 2.6 g) of ethyl 2-[6-(bromomethyl)-7-chloro-2-oxo-4-phenyl-2H-chromen-3-yl]acetate. The crude crystal was dissolved in acetic acid (50 ml) and concentrated hydrochloric acid (25 ml), and heated under reflux for 30 minutes. The reaction solution was concentrated under reduced pressure, and the resultant residue was dissolved in a solvent mixture of THF (10 ml) and ethyl acetate (50 ml), and then washed with water followed by a saturated aqueous solution of sodium hydrogen carbonate and a saturated aqueous solution of sodium chloride. After drying over magnesium sulfate, the solvent was distilled off under reduced pressure, and the residue was washed with ethyl acetate to obtain a crude crystal (1.78 g, yield: 44%) of the title compound. The compound was used in the next reaction without further purification. NMR (CDCl3) δ: 3.43 (2H, s), 4.58 (2H, s), 7.11 (1H, s), 7.20-7.30 (2H, m), 7.48 (1H, s), 7.50-7.65 (3H, m).

Workup

  1. temperatureheated
  2. temperatureunder reflux for 1 hour
  3. temperatureAfter cooling
  4. washthe reaction solution was washed with water
  5. dry with materialAfter drying over magnesium sulfate
  6. distillationthe solvent was distilled off under reduced pressure
  7. customthe residue was purified by a silica gel column chromatography (eluent: ethyl acetate-hexane=1:4)
  8. customto obtain the crude crystal (approximately 2.6 g) of ethyl 2-[6-(bromomethyl)-7-chloro-2-oxo-4-phenyl-2H-chromen-3-yl]acetate
  9. temperatureunder reflux for 30 minutes
  10. concentrationThe reaction solution was concentrated under reduced pressure
  11. dissolutionthe resultant residue was dissolved in a solvent mixture of THF (10 ml) and ethyl acetate (50 ml)
  12. washwashed with water
  13. dry with materialAfter drying over magnesium sulfate
  14. distillationthe solvent was distilled off under reduced pressure
  15. washthe residue was washed with ethyl acetate

Sources & evidence

ORD record
ord-7c9cd02d2cbd4a3a9bf3ff5f8c302a48
Source dataset
uspto-grants-2005_12
Patent number
US06974806B2

Reaction notes

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