Phosphorus oxybromide → Methyl 4-bromo-8-fluoro-7-methylquinoline-2-carboxylate

HRID 922804Notes

Reaction equation

HRID 922804 reaction equation
[F:1][C:2]1[C:3]([CH3:17])=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]([O:14][CH3:15])=[O:13])[CH:8]=[C:7]2O.P(Br)(Br)([Br:20])=O>C1(C)C=CC=CC=1.CC#N>[Br:20][C:7]1[C:6]2[C:11](=[C:2]([F:1])[C:3]([CH3:17])=[CH:4][CH:5]=2)[N:10]=[C:9]([C:12]([O:14][CH3:15])=[O:13])[CH:8]=1

Participants

5

Reactant 2

HCID 24613Phosphorus oxybromideHCID 178498502HCID 178498502, compound

Product 1

HCID 89543904Methyl 4-bromo-8-fluoro-7-methylquinoline-2-carboxylateYield 66.5%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of (methyl 8-fluoro-4-hydroxy-7-methylquinoline-2-carboxylate (7-15, 842.1 mg, 3.58 mmol) and POBr3 (1129 mg, 3.94 mmol) in Toluene (8.14 mL) and CH3CN (0.81 mL) was heated at 75° C. for 1 h. After cooling to room temperature, the mixture was poured to a mixture of ice-H2O, followed by CH2Cl2 extraction (twice). The combined organic fractions were dried (Na2SO4), filtered and the solvent was evaporated under reduced pressure. The residue was purified by silica gel flash chromatography (gradient 0-50% EtOAc/Hexanes) to afford methyl 4-bromo-8-fluoro-7-methylquinoline-2-carboxylate (7-16, 710 mg). LRMS m/z (M+H)+ 298.1 found, 298.0 required.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionfollowed by CH2Cl2 extraction (twice)
  3. dry with materialThe combined organic fractions were dried (Na2SO4)
  4. filtrationfiltered
  5. customthe solvent was evaporated under reduced pressure
  6. customThe residue was purified by silica gel flash chromatography (gradient 0-50% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-e28b63ac80c94edc9429f5408feaf569
Source dataset
uspto-grants-2016_03
Patent number
US09278960B2

Reaction notes

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