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

HRID 216875Notes

Reaction equation

HRID 216875 reaction equation
Br[CH2:2][C:3]1[C:12]([C:13]2[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=2[Cl:20])=[N:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[Cl:21])[N:4]=1.I([O-])(=O)(=O)=[O:23].[Na+].CN(C=O)C>CCOC(C)=O>[Cl:21][C:9]1[CH:8]=[CH:7][CH:6]=[C:5]2[C:10]=1[N:11]=[C:12]([C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=1[Cl:20])[C:3]([CH:2]=[O:23])=[N:4]2

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 23667635Sodium periodateHCID 577078212-(Bromomethyl)-5-chloro-3-(2-chloro-5-fluorophenyl)quinoxaline

Product 1

HCID 577077675-Chloro-3-(2-chloro-5-fluorophenyl)quinoxaline-2-carbaldehyde

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 2-(bromomethyl)-5-chloro-3-(2-chloro-5-fluorophenyl)quinoxaline (Prepared in Example 100, 0.5625 g, 1.457 mmol) and sodium metaperiodate (0.1613 mL, 2.914 mmol) in DMF (9.714 mL, 1.457 mmol) was heated at 150° C. with stirring. After 3 h, the mixture was cooled to room temperature, diluted with EtOAc (100 mL), washed with 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 3 min as eluent to give 5-chloro-3-(2-chloro-5-fluorophenyl)quinoxaline-2-carbaldehyde as an off-white solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 10.16 (1H, s), 8.35-8.41 (1H, m), 8.29-8.34 (1H, m), 8.07 (1H, dd, J=8.4, 7.6 Hz), 7.68 (1H, dd, J=8.8, 4.9 Hz), 7.44-7.58 (2H, m); LC-MS (ESI) m/z 321.0 [M+H]+.

Workup

  1. temperaturethe mixture was cooled to room temperature
  2. washwashed with 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-573837666271426b8ca20ba148435446
Source dataset
uspto-grants-2012_06
Patent number
US08193199B2

Reaction notes

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