5-Acetyl-8-(benzyloxy)-1,2-dihydroquinolin-2-one → 8-Benzyloxy-5-(2-bromoacetyl)-2-hydroxyquinoline

HRID 2205681Notes

Reaction equation

HRID 2205681 reaction equation
[C:1]([C:4]1[CH:13]=[CH:12][C:11]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:10]2[C:5]=1[CH:6]=[CH:7][C:8](=[O:22])[NH:9]2)(=[O:3])[CH3:2].[Br-:23].[Br-].[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C([N+](CCCC)(CCCC)CCCC)CCC.C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1.CO>[CH2:15]([O:14][C:11]1[CH:12]=[CH:13][C:4]([C:1](=[O:3])[CH2:2][Br:23])=[C:5]2[C:10]=1[NH:9][C:8](=[O:22])[CH:7]=[CH:6]2)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

5

Reactant 2

HCID 133754445-Acetyl-8-(benzyloxy)-1,2-dihydroquinolin-2-oneHCID 23500184Tetra-n-butylammonium tribromide

Product 1

HCID 116678678-Benzyloxy-5-(2-bromoacetyl)-2-hydroxyquinolineYield 73%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of 5-acetyl-8-(benzyloxy)quinolin-2(1H)-one (19.4 g, 66.4 mmol) in anhydrous THF (240 mL) and anhydrous methanol (165 mL) was added a solution of tetra-n-butylammonium tribromide (Bu4NBr3) (54.5 g, 113.0 mmol) in anhydrous THF (130 mL) dropwise over 1.5 hours. The resulting solution was stirred at RT overnight before concentrating under reduced pressure without heating. The residue was re-dissolved in methanol (200 mL). Saturated aqueous ammonium chloride solution (390 mL) was added with ice-cooling. The resulting suspension was filtered and the solid washed with water and air-dried under vacuum. The solid was suspended in DCM and methanol (1:1 v/v, 100 mL) for 90 minutes. The solid was collected by filtration, washed with DCM and air-dried to afford the title compound (18.0 g, 73%). 1H NMR (400 MHz, DMSO-d6): δ 11.07 (s, 1H); 8.51 (d, J=10.0 Hz, 1H); 7.94-7.83 (m, 1H); 7.60 (d, J=7.5 Hz, 2H); 7.44-7.27 (m, 4H); 6.79-6.65 (m, 1H); 5.53-5.39 (s, 2H); 4.93 (s, 2H)

Workup

  1. concentrationbefore concentrating under reduced pressure
  2. temperaturewithout heating
  3. dissolutionThe residue was re-dissolved in methanol (200 mL)
  4. additionSaturated aqueous ammonium chloride solution (390 mL) was added with ice-
  5. temperaturecooling
  6. filtrationThe resulting suspension was filtered
  7. washthe solid washed with water
  8. customair-dried under vacuum
  9. waitmethanol (1:1 v/v, 100 mL) for 90 minutes
  10. filtrationThe solid was collected by filtration
  11. washwashed with DCM
  12. customair-dried

Sources & evidence

ORD record
ord-076a359b3fa14dd197e44b45833db20c
Source dataset
uspto-grants-2016_06
Patent number
US09371318B2

Reaction notes

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