Diethyl Ether → 1-(5-Chloro-3-(2-chloro-5-fluorophenyl)quinoxalin-2-yl)ethanol

HRID 1397789Notes

Reaction equation

HRID 1397789 reaction equation
[Cl:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[N:4]=[C:5]([C:14]1[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=1[Cl:21])[C:6]([CH:12]=[O:13])=[N:7]2.[CH2:22]1COCC1.C[Mg]Br.C(OCC)C>>[Cl:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[N:4]=[C:5]([C:14]1[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=1[Cl:21])[C:6]([CH:12]([OH:13])[CH3:22])=[N:7]2

Participants

5

Reactant 4

HCID 3283Diethyl EtherHCID 8028TetrahydrofuranHCID 577077675-Chloro-3-(2-chloro-5-fluorophenyl)quinoxaline-2-carbaldehydeHCID 178418573HCID 178418573, compound

Product 1

HCID 577079211-(5-Chloro-3-(2-chloro-5-fluorophenyl)quinoxalin-2-yl)ethanol

Procedure

To a stirring heterogeneous mixture of 5-chloro-3-(2-chloro-5-fluorophenyl)-quinoxaline-2-carbaldehyde (0.1650 g, 0.514 mmol) in THF (5.00 mL, 0.514 mmol) was added methylmagnesium bromide 3 M in diethyl ether (0.257 mL, 0.771 mmol) dropwise at 0° C., and the mixture was then allowed to warm to room temperature and stirred at room temperature. After 5.5 h, the reaction was quenched with NH4Cl (50 mL) and extracted with EtOAc (50 mL×2). The combined organic layers were washed with water (50 mL×1), brine (50 mL×1), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue 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 1-(5-chloro-3-(2-chloro-5-fluorophenyl)quinoxalin-2-yl)ethanol as a solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.17 (1 H, dd, J=8.4, 1.4 Hz), 8.09 (1 H, dd, J=7.8, 1.2 Hz), 7.88-7.96 (1 H, m), 7.72 (1 H, dd, J=9.0, 5.1 Hz), 7.61 (1 H, br. s.), 7.44-7.53 (1 H, m), 5.36 (1 H, d, J=6.3 Hz), 4.83 (1 H, br. s.), 1.49 (3 H, br. s.); LC-MS (ESI) m/z 337.0 [M+]+.

Workup

  1. customthe reaction was quenched with NH4Cl (50 mL)
  2. extractionextracted with EtOAc (50 mL×2)
  3. washThe combined organic layers were washed with water (50 mL×1), brine (50 mL×1)
  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 40 g of Redi-Sep™ column
  8. customover 14 min

Sources & evidence

ORD record
ord-e56a55e8002f4011944fcaab043b4ad6
Source dataset
uspto-grants-2014_12
Patent number
US08901135B2

Reaction notes

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