Carbonic Acid → 5-Chloro-3-(3-fluorophenyl)-2-methylquinoxaline

HRID 216864Notes

Reaction equation

HRID 216864 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]1[CH:16]=[C:17](B(O)O)[CH:18]=[CH:19][CH:20]=1.C(O)(O)=O>CC#N.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:12][C:9]1[CH:8]=[CH:7][CH:6]=[C:5]2[C:10]=1[N:11]=[C:2]([C:19]1[CH:18]=[CH:17][CH:16]=[C:15]([F:14])[CH:20]=1)[C:3]([CH3:13])=[N:4]2

Participants

6

Reactant 3

HCID 767Carbonic AcidHCID 27339863-Fluorophenylboronic acidHCID 577078723-Chloro-5-chloro-2-methylquinoxaline

Product 1

HCID 577078545-Chloro-3-(3-fluorophenyl)-2-methylquinoxaline

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

A mixture of 3,5-dichloro-2-methylquinoxaline (Prepared in Example 85, 0.3361 g, 1.577 mmol), 3-fluorobenzeneboronic acid (0.2428 g, 1.735 mmol), tetrakis(triphenylphosphine)palladium (0.09114 g, 0.07887 mmol), and sodium carbonate anhydrous (0.8360 g, 7.887 mmol) in CH3CN—H2O (3:1) (16.00 mL) was stirred at 100° C. After 3.5 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×2), dried over Na2SO4, filtered, and concentrated under reduced pressure to give red syrup. The red syrup was purified by silica gel column chromatography on a 40 g of Redi-Sep™ column using 0 to 50% gradient of EtOAc in hexane over 14 min and then 50% isocratic of EtOAc for 10 min as eluent to give 5-chloro-3-(3-fluorophenyl)-2-methylquinoxaline as a solid: 1H NMR (400 MHz, DMF) δ ppm 8.05 (1H, dd, J=8.4, 1.4 Hz), 8.00 (1H, dd, J=7.6, 1.4 Hz), 7.83 (1H, dd, J=8.4, 7.6 Hz), 7.60-7.67 (3H, m), 7.38-7.46 (1H, m), 2.74 (3H, s); LC-MS (ESI) m/z 273.1 [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×2)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto give red syrup
  8. customThe red syrup was purified by silica gel column chromatography on a 40 g of Redi-Sep™ column
  9. customover 14 min

Sources & evidence

ORD record
ord-438208b83fd04e33b81adc5715e81e30
Source dataset
uspto-grants-2012_06
Patent number
US08193199B2

Reaction notes

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