Carbonic Acid → 5-Chloro-2-methyl-3-(2-(trifluoromethyl)phenyl)quinoxaline

HRID 1397753Notes

Reaction equation

HRID 1397753 reaction equation
Cl[C:2]1[C:3]([CH3:13])=[N:4][C:5]2[C:10]([N:11]=1)=[C:9]([Cl:12])[CH:8]=[CH:7][CH:6]=2.[F:14][C:15]([F:26])([F:25])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1B(O)O.C(O)(O)=O>CC#N.O>[Cl:12][C:9]1[CH:8]=[CH:7][CH:6]=[C:5]2[C:10]=1[N:11]=[C:2]([C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[C:15]([F:26])([F:25])[F:14])[C:3]([CH3:13])=[N:4]2

Participants

5

Reactant 3

HCID 767Carbonic AcidHCID 27343872-(Trifluoromethyl)benzeneboronic acidHCID 577078723-Chloro-5-chloro-2-methylquinoxaline

Product 1

HCID 577079875-Chloro-2-methyl-3-(2-(trifluoromethyl)phenyl)quinoxaline

Reagents, catalysts & solvents 1

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

Conditions

Temperature
100 °C

Procedure

A mixture of 3,5-dichloro-2-methylquinoxaline (1.1209 g, 5.261 mmol), 2-(trifluoromethyl)phenylboronic acid (1.099 g, 5.787 mmol), tetrakis(triphenyl-phosphine)palladium (0.3040 g, 0.2630 mmol), and sodium carbonate anhydrous (2.788 g, 26.30 mmol) in 53 mL of CH3CN—H2O (3:1) was stirred at 100° C. After 13.5 h, the mixture was cooled to room temperature and partitioned between EtOAc (100 mL) and water (100 mL). The organic layer was washed with brine (50 mL×3), dried over Na2SO4, filtered, and concentrated under reduced pressure to give a red syrup. The red syrup 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 20 min as eluent to give 5-chloro-2-methyl-3-(2-(trifluoromethyl)phenyl)quinoxaline as a red solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.09 (1 H, dd, J=8.4, 1.4 Hz), 8.02 (1 H, dd, J=7.6, 1.2 Hz), 7.98 (1 H, d, J=7.8 Hz), 7.73-7.92 (4 H, m), 2.47 (3 H, s); LC-MS (ESI) m/z 323.0 [M+H]+.

Workup

  1. temperaturethe mixture was cooled to room temperature
  2. custompartitioned between EtOAc (100 mL) and water (100 mL)
  3. washThe organic layer was washed with brine (50 mL×3)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto give a red syrup
  8. customThe red syrup was purified by silica gel column chromatography on a 80 g of Redi-Sep™ column
  9. customover 25 min

Sources & evidence

ORD record
ord-63c5543af60b4b04a3a25e4aa3933426
Source dataset
uspto-grants-2014_12
Patent number
US08901135B2

Reaction notes

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