Sulfuryl chloride → 8-(2-Chloro-6-fluoro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid ethyl ester

HRID 1189863Notes

Reaction equation

HRID 1189863 reaction equation
S(Cl)([Cl:4])(=O)=O.[CH2:6]([O:8][C:9]([C:11]1[C:12]2[N:13]=[CH:14][CH:15]=[N:16][C:17]=2[C:18]([C:21]2[C:26]([F:27])=[C:25]([O:28][CH3:29])[CH:24]=[C:23]([O:30][CH3:31])[C:22]=2F)=[CH:19][CH:20]=1)=[O:10])[CH3:7]>CC#N>[CH2:6]([O:8][C:9]([C:11]1[C:12]2[N:13]=[CH:14][CH:15]=[N:16][C:17]=2[C:18]([C:21]2[C:26]([F:27])=[C:25]([O:28][CH3:29])[CH:24]=[C:23]([O:30][CH3:31])[C:22]=2[Cl:4])=[CH:19][CH:20]=1)=[O:10])[CH3:7]

Participants

4

Reactant 2

HCID 24648Sulfuryl chlorideHCID 866411458-(2,6-Difluoro-3,5-dimethoxyphenyl)quinoxaline-5-carboxylic acid ethyl ester

Product 1

HCID 866411468-(2-Chloro-6-fluoro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid ethyl esterYield 82.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

Sulfuryl chloride (0.35 mL, 4.33 mmol, 1.1 equiv) in CH3CN (10 mL) was added dropwise to a cold (−30° C.) solution of 8-(2,6-difluoro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid ethyl ester (Step 143.1) (1.4 g, 3.93 mmol) in CH3CN (40 mL). The reaction mixture was quenched by addition of a saturated solution of NaHCO3, allowed to warm to rt and concentrated. The residue was diluted in EtOAc and a saturated solution of NaHCO3. The aqueous phase was separated and extracted with EtOAc. The combined organic layers were washed with H2O and brine, dried (Na2SO4), filtered and concentrated. The residue was purified by silica gel column chromatography (Hex/EtOAc, 3:2) to provide 1.27 g of the title compound as a white solid. Title compound: ESI-MS: 391.1 [M+H]+; tR=4.71 min (System 1); TLC: Rf=0.12 (Hex/EtOAc, 3:2).

Workup

  1. customThe reaction mixture was quenched by addition of a saturated solution of NaHCO3
  2. concentrationconcentrated
  3. additionThe residue was diluted in EtOAc
  4. customThe aqueous phase was separated
  5. extractionextracted with EtOAc
  6. washThe combined organic layers were washed with H2O and brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by silica gel column chromatography (Hex/EtOAc, 3:2)

Sources & evidence

ORD record
ord-e669f85e0f9442deae9e67b171c2f887
Source dataset
uspto-grants-2014_03
Patent number
US08674099B2

Reaction notes

Loading…