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Ethyl Acetate → 9-Chloro-2,2,4-trimethyl-1,4-dihydro-2H-6-oxa-1,4-diazachrysen-3,5-dione

HRID 1038476
Notes
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Reaction equation

HRID 1038476 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:26]C)=[C:6]([C:8]2[C:17]([C:18](OC)=[O:19])=[C:16]3[C:11]([NH:12][C:13]([CH3:25])([CH3:24])[C:14](=[O:23])[N:15]3[CH3:22])=[CH:10][CH:9]=2)[CH:7]=1.B(Br)(Br)Br.C(OCC)(=O)C.[H-].[Na+]>ClCCl.O.C(OCC)C>[Cl:1][C:2]1[CH:7]=[C:6]2[C:5]([O:26][C:18](=[O:19])[C:17]3[C:8]2=[CH:9][CH:10]=[C:11]2[C:16]=3[N:15]([CH3:22])[C:14](=[O:23])[C:13]([CH3:25])([CH3:24])[NH:12]2)=[CH:4][CH:3]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 8857Ethyl Acetate2×HCID 24758Sodium hydride2×HCID 25134Boron tribromideHCID 247809987-(5-Chloro-2-methoxyphenyl)-8-methoxycarbonyl-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one

Product 1

HCID 576717409-Chloro-2,2,4-trimethyl-1,4-dihydro-2H-6-oxa-1,4-diazachrysen-3,5-dioneYield 61%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

7-(5-Chloro-2-methoxyphenyl)-8-methoxycarbonyl-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one (Reference Compound No. 10-1, 3.81 g, 9.80 mmol) was dissolved in anhydrous dichloromethane (30 mL), boron tribromide (7.62 g, 30.4 mmol) was added thereto at −78° C., and then stirred at room temperature for 1 hour. The reaction mixture was poured into ice water (500 mL), ethyl acetate (500 mL) was added thereto and partitioned. The organic layer was washed with saturated brine (200 mL), dried over anhydrous magnesium sulfate, and then the solvent was removed under reduced pressure. The obtained residue was dissolved in N,N-dimethylformamide (50 mL), 60% sodium hydride (23.1 mg, 0.578 mmol) was added thereto, and then stirred at 70° C. overnight. 60% sodium hydride (31.2 mg, 0.780 mmol) was added more thereto and stirred at 80° C. overnight. After cooling down, ethyl acetate (200 mL), diethylether (200 mL) and water (300 mL) were added and partitioned. The organic layer was washed with water (200 mL) and saturated brine (200 mL) successively, dried over anhydrous magnesium sulfate, and then the solvent was removed under reduced pressure. The obtained residue was filtered with ethyl acetate/hexane (¼, 30 mL) to give the titled reference compound (2.04 g) as a pale yellow solid. (Yield 61%)

Workup

  1. additionwas added
  2. custompartitioned
  3. washThe organic layer was washed with saturated brine (200 mL)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customthe solvent was removed under reduced pressure
  6. dissolutionThe obtained residue was dissolved in N,N-dimethylformamide (50 mL)
  7. stirringstirred at 70° C. overnight
  8. stirringstirred at 80° C. overnight
  9. temperatureAfter cooling down
  10. custompartitioned
  11. washThe organic layer was washed with water (200 mL) and saturated brine (200 mL) successively
  12. dry with materialdried over anhydrous magnesium sulfate
  13. customthe solvent was removed under reduced pressure
  14. filtrationThe obtained residue was filtered with ethyl acetate/hexane (¼, 30 mL)

Sources & evidence

ORD record
ord-532d514be7714f65befcb251a9099299
Source dataset
uspto-grants-2013_10
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08551991B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes