Sulfuric Acid → (6-Chloro-3-methyl-quinoxalin-5-yl)-acetic acid methyl ester

HRID 505233Notes

Reaction equation

[CH3:1][O-:2].[Na+].[Cl:4][C:5]1[C:14]([CH2:15][C:16](Cl)(Cl)Cl)=[C:13]2[C:8]([N:9]=[CH:10][C:11]([CH3:20])=[N:12]2)=[CH:7][CH:6]=1.S(=O)(=O)(O)[OH:22]>CO>[CH3:1][O:2][C:16](=[O:22])[CH2:15][C:14]1[C:5]([Cl:4])=[CH:6][CH:7]=[C:8]2[C:13]=1[N:12]=[C:11]([CH3:20])[CH:10]=[N:9]2

Participants

Conditions

Temperature: 70 °C

Procedure

NaOMe (5.4 M in MeOH, 8.3 ml, 44.71 mmol, 4.5 equiv) was added at room temperature to a solution of 7-chloro-2-methyl-8-(2,2,2-trichloro-ethyl)-quinoxaline (3.08 g, 9.94 mmol) in methanol (24 ml). The reaction mixture was heated to 70° C. for 3 hours. After cooling to 0° C., sulfuric acid (4.7 ml) dissolved in methanol (20 ml) was added, and the reaction mixture was heated to 70° C. for one hour. After cooling and dilution with EtOAc and H2O, the mixture was filtered and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified via flash chromatography (gradient of hexane/EtOAc 100:0 to 70:30) to afford the title compound (1.14 g, 46%) as a solid. 1H NMR (400 MHz, CDCl3): δ=8.70 (s, 1H), 7.95 (d, J=9.1 Hz, 1H), 7.69 (d, J=9.1 Hz, 1H), 4.48 (s, 2H), 3.70 (s, 3H), 2.74 (s, 3H). MS (ES+): 251.1 (M+H)+.

Workup

temperatureAfter cooling to 0° C.
additionwas added
temperaturethe reaction mixture was heated to 70° C. for one hour
temperatureAfter cooling
filtrationdilution with EtOAc and H2O, the mixture was filtered
extractionextracted with EtOAc
washThe combined organic layers were washed with brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified via flash chromatography (gradient of hexane/EtOAc 100:0 to 70:30)

Sources & evidence

ORD record: ord-abc3f11a017b452a8663eef581150d12
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07781438B2

Reaction notes

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