Ethyl Acetate → 5-Bromo-2-chloro-8-methoxyquinoline

HRID 1423097Notes

Reaction equation

HRID 1423097 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:12]=1[N:11]=[C:10]([Cl:13])[CH:9]=[CH:8]2.[Br:14]Br.[O-]S([O-])(=S)=O.[Na+].[Na+].CCOC(C)=O>CO>[Br:14][C:6]1[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[C:12]2[C:7]=1[CH:8]=[CH:9][C:10]([Cl:13])=[N:11]2

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 24408BromineHCID 24477Sodium ThiosulfateHCID 35852672-Chloro-8-methoxyquinoline

Product 1

HCID 581890975-Bromo-2-chloro-8-methoxyquinolineYield 49%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

A solution of 8-methoxy-2-(chloro)quinoline CAS [74668-74-9] (1.0 g, 4.4 mmol) in MeOH (6.25 mL) was treated with a 1.5 N solution of bromine in MeOH (3.53 mL, 5.3 mmol) over 15 min period. The reaction mixture was stirred 2 h, treated with a 1 N aqueous Na2S2O3 solution (20 mL) followed by EtOAc (100 mL). The organic portion was washed with brine followed by a saturated aqueous solution of NaHCO3 followed by brine. The organic phase was dried over Na2SO4, filtered, evaporated, and purified by silica gel chromatography eluting with CH2Cl2 to afford titled compound as a colorless solid (49%). 1H NMR (CDCl3) 8.44 (dd, J=8.8, 1.2, 1H), 7.73 (dd, J=8.4, 1.2, 1H), 7.51 (dd, J=8.8, 1.2, 1 H), 6.97 (d, J=8.4, 1H), 4.06 (s, 3H). LC/MS 3.45 min, [M+1]+ 271/273.

Workup

  1. washThe organic portion was washed with brine
  2. dry with materialThe organic phase was dried over Na2SO4
  3. filtrationfiltered
  4. customevaporated
  5. custompurified by silica gel chromatography
  6. washeluting with CH2Cl2

Sources & evidence

ORD record
ord-631328218802487fa61c6d16c07fac0e
Source dataset
uspto-grants-2015_01
Patent number
US08927546B2

Reaction notes

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