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

HRID 216872Notes

Reaction equation

HRID 216872 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.[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=1B(O)O.C(O)(O)=O>C(#N)C.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:20]1[CH:19]=[C:18]([F:21])[CH:17]=[CH:16][C:15]=1[Cl:14])[C:3]([CH3:13])=[N:4]2

Participants

6

Reactant 3

HCID 767Carbonic AcidHCID 226481162-Chloro-5-fluorobenzeneboronic acidHCID 577078723-Chloro-5-chloro-2-methylquinoxaline

Product 1

HCID 577077525-Chloro-3-(2-chloro-5-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, 1.0000 g, 4.693 mmol), 2-chloro-5-fluorophenylboronic acid (0.9002 g, 5.163 mmol), tetrakis(triphenylphosphine)palladium (0.2712 g, 0.2347 mmol), and sodium carbonate anhydrous (2.487 g, 23.47 mmol) in acetonitrile-water (3:1) (47.00 mL) was stirred at 100° C. After 3 hs, 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. The residue 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 10 min as eluent to give 5-chloro-3-(2-chloro-5-fluorophenyl)-2-methylquinoxaline as a red syrupy solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.09 (1H, dd, J=8.4, 1.4 Hz), 8.03 (1H, dd, J=7.6, 1.4 Hz), 7.88 (1H, dd, J=8.4, 7.6 Hz), 7.75 (1H, dd, J=9.0, 5.1 Hz), 7.61 (1H, dd, J=8.6, 3.1 Hz), 7.46-7.53 (1H, m), 2.54 (3H, s); LC-MS (ESI) m/z 307.0 [M+H]+.

Workup

  1. temperatureAfter 3 hs, the 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. customThe residue was purified by silica gel column chromatography on a 80 g of Redi-Sep™ column
  8. customover 25 min

Sources & evidence

ORD record
ord-64eb93b21ef54c14a0bb78de06f65eff
Source dataset
uspto-grants-2012_06
Patent number
US08193199B2

Reaction notes

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