Carbonic Acid → 2-(3-Fluorophenyl)-8-methoxyquinoline-3-carbaldehyde

HRID 216854Notes

Reaction equation

HRID 216854 reaction equation
Cl[C:2]1[C:11]([CH:12]=[O:13])=[CH:10][C:9]2[C:4](=[C:5]([O:14][CH3:15])[CH:6]=[CH:7][CH:8]=2)[N:3]=1.[F:16][C:17]1[CH:18]=[C:19](B(O)O)[CH:20]=[CH:21][CH:22]=1.C(O)(O)=O>CC#N.O>[F:16][C:17]1[CH:22]=[C:21]([C:2]2[C:11]([CH:12]=[O:13])=[CH:10][C:9]3[C:4](=[C:5]([O:14][CH3:15])[CH:6]=[CH:7][CH:8]=3)[N:3]=2)[CH:20]=[CH:19][CH:18]=1

Participants

5

Reactant 3

HCID 767Carbonic AcidHCID 27339863-Fluorophenylboronic acidHCID 125186352-Chloro-8-methoxyquinoline-3-carbaldehyde

Product 1

HCID 577080272-(3-Fluorophenyl)-8-methoxyquinoline-3-carbaldehyde

Reagents, catalysts & solvents 1

HCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-chloro-8-methoxyquinoline-3-carbaldehyde (1.8583 g, 8.384 mmol), 3-fluorobenzeneboronic acid (1.290 g, 9.223 mmol), tetrakis(tri-phenylphosphine)palladium (0.4844 g, 0.4192 mmol), and sodium carbonate anhydrous (4.443 g, 41.92 mmol) in 76 mL of CH3CN—H2O (3:1) was stirred at 100° C. After 3 h, the mixture was cooled to room temperature and partitioned between EtOAc (200 mL) and water (100 mL). The organic layer was washed with brine (100 mL×2), dried over Na2SO4, filtered, and concentrated under reduced pressure to give an orange solid. The orange solid was purified by silica gel column chromatography on a 80 g of Redi-Sep™ column using 0 to 50% gradient of EtOAc in hexane over 25 min and then 50% isocratic of EtOAc for 25 min as eluent to give 2-(3-fluorophenyl)-8-methoxyquinoline-3-carbaldehyde as a light-yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 10.09 (1H, s), 8.94 (1H, s), 7.80 (1H, dd, J=8.2, 1.2 Hz), 7.66 (1H, t, J=8.0 Hz), 7.53-7.64 (2H, m), 7.47-7.53 (1H, m), 7.36-7.44 (2H, m), 4.00 (3H, s); LC-MS (ESI) m/z 282.1 [M+H]+.

Workup

  1. temperaturethe mixture was cooled to room temperature
  2. custompartitioned between EtOAc (200 mL) and water (100 mL)
  3. washThe organic layer was washed with brine (100 mL×2)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto give an orange solid
  8. customThe orange solid was purified by silica gel column chromatography on a 80 g of Redi-Sep™ column
  9. customover 25 min

Sources & evidence

ORD record
ord-b86ec485a6044e34ac7f1c9ff878e48b
Source dataset
uspto-grants-2012_06
Patent number
US08193199B2

Reaction notes

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