Hydrochloric Acid → 3-(4-Fluoro-2-methoxy-phenoxy)quinoxaline-2-carboxylic acid

HRID 2280570Notes

Reaction equation

Cl[C:2]1[C:3]([C:12]([O:14]CC)=[O:13])=[N:4][C:5]2[C:10]([N:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2.[F:17][C:18]1[CH:23]=[CH:22][C:21]([OH:24])=[C:20]([O:25][CH3:26])[CH:19]=1.C([O-])([O-])=O.[Cs+].[Cs+].Cl>CN1C(=O)CCC1.O>[F:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][C:2]2[C:3]([C:12]([OH:14])=[O:13])=[N:4][C:5]3[C:10]([N:11]=2)=[CH:9][CH:8]=[CH:7][CH:6]=3)=[C:20]([O:25][CH3:26])[CH:19]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of ethyl 3-chloroquinoxaline-2-carboxylate (300 mg, 1.27 mmol), 4-fluoro-2-methoxy-phenol (289.0 μL, 2.54 mmol) and Cs2CO3 (826.3 mg, 2.54 mmol) in NMP (3.0 mL) was stirred at 100° C. for 3 hours. The reaction mixture was poured into water, the pH was adjusted to pH 6 with 1N HCl and the mixture was extracted with ethyl acetate (3×). The organics were combined, washed with brine, dried with Na2SO4, filtered and evaporated to dryness. Purification by column chromatography using a gradient of 0-10% MeOH in dichloromethane gave 3-(4-fluoro-2-methoxy-phenoxy)quinoxaline-2-carboxylic acid (360 mg, 90%) as a red oil. ESI-MS m/z calc. 314.07, found 315.1 (M+1)+; Retention time: 1.35 minutes (3 minutes run).

Workup

extractionthe mixture was extracted with ethyl acetate (3×)
washwashed with brine
dry with materialdried with Na2SO4
filtrationfiltered
customevaporated to dryness
customPurification by column chromatography

Sources & evidence

ORD record: ord-84d11d61c334459ca8d1995b3ac1e310
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09139529B2

Reaction notes

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