Dimethylformamide → 5-Chloro-3-(3-fluorophenyl)quinoxaline-2-carbaldehyde

HRID 216882Notes

Reaction equation

HRID 216882 reaction equation
Br[CH2:2][C:3]1[C:12]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[CH:14]=2)=[N:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[Cl:20])[N:4]=1.I([O-])(=O)(=O)=[O:22].[Na+].CN(C=O)C>CCOC(C)=O>[Cl:20][C:9]1[CH:8]=[CH:7][CH:6]=[C:5]2[C:10]=1[N:11]=[C:12]([C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[CH:14]=1)[C:3]([CH:2]=[O:22])=[N:4]2

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 23667635Sodium periodateHCID 577078502-(Bromomethyl)-5-chloro-3-(3-fluorophenyl)quinoxaline

Product 1

HCID 577078765-Chloro-3-(3-fluorophenyl)quinoxaline-2-carbaldehyde

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 2-(bromomethyl)-5-chloro-3-(3-fluorophenyl)quinoxaline (Prepared in Example 95, 0.8089 g, 2.301 mmol) and sodium metaperiodate (0.9842 g, 4.601 mmol) in DMF (15.34 mL, 2.301 mmol) was heated at 150° C. with stirring. After 5 h, the mixture was cooled to room temperature, diluted with EtOAc (100 mL), washed with sat'd Na2S2O3 (50 mL×1) and brine (50 mL×2), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography on a 80 g of Redi-Sep™ column using 0 to 10% gradient of EtOAc in hexane over 10 min, then 10% isocratic of EtOAc for 20 min, then 10 to 20% gradient of EtOAc in hexane over 20 min, then 20% isocratic of EtOAc for 20 min as eluent to give 5-chloro-3-(3-fluorophenyl)quinoxaline-2-carbaldehyde as a solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 10.18 (1H, s), 8.31 (1H, dd, J=8.2, 1.2 Hz), 8.25 (1H, dd, J=7.4, 1.2 Hz), 7.99 (1H, dd, J=8.4, 7.6 Hz), 7.56-7.70 (3H, m), 7.38-7.46 (1H, m); LC-MS (ESI) m/z 287.0 [M+H]+.

Workup

  1. temperaturethe mixture was cooled to room temperature
  2. washwashed with sat'd Na2S2O3 (50 mL×1) and brine (50 mL×2)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography on a 80 g of Redi-Sep™ column
  7. customover 10 min
  8. wait10% isocratic of EtOAc for 20 min
  9. wait10 to 20% gradient of EtOAc in hexane over 20 min

Sources & evidence

ORD record
ord-819f52f5c9ae4b318197897148c2429e
Source dataset
uspto-grants-2012_06
Patent number
US08193199B2

Reaction notes

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