Hydrogen Peroxide → 8-bromo-7-fluoro-3-methylquinoxalin-2(1H)-one

HRID 1056100Notes

Reaction equation

O.OO.[Br:4][C:5]1[C:6]([F:17])=[CH:7][CH:8]=[C:9]2[C:14]=1[NH:13][C:12](=[O:15])[CH:11]([CH3:16])[NH:10]2.[OH-].[Na+]>CO>[Br:4][C:5]1[C:6]([F:17])=[CH:7][CH:8]=[C:9]2[C:14]=1[NH:13][C:12](=[O:15])[C:11]([CH3:16])=[N:10]2

Participants

Conditions

Temperature: 85 °C

Procedure

A mixture of water (14 mL) and 30% H2O2 (30.0 mL, 294 mmol) was added slowly dropwise to a solution of 8-bromo-7-fluoro-3-methyl-3,4-dihydroquinoxalin-2(1H)-one (600e) (21.7 g, 84 mmol) in 1 N NaOH (168 mL, 168 mmol) and MeOH (140 mL). The flask was fitted with a reflux condenser and heated at 85° C. for 3 h. LC-MS indicated ca. 87% conversion to the desired product (M+1=257.0/259.0). The reaction mixture was cooled to RT and acidified with 2 N HCl to ca. pH 6 and was diluted with CHCl3/IPA(4:1) (100 mL), added to a separatory funnel. The resulting suspension was filtered through a sintered glass frit, washing with water and dried affording 8-bromo-7-fluoro-3-methylquinoxalin-2(1H)-one (5.83 g, 22 mmol, 22% yield) as a light brown solid. m/z (ESI, +ve ion) 257.0/259.0 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.83 (1H, br. s.), 7.67-7.88 (1H, m), 7.34 (1H, t, J=8.4 Hz), 2.43 (3H, s). 19F NMR (377 MHz, DMSO-d6) δ ppm −104.13 (1F, s). The aq. solution was extracted with CHCl3:i-PrOH 9:1 (6×100 mL), dried over MgSO4, filtered and concentrated affording additional 8-bromo-7-fluoro-3-methylquinoxalin-2(1H)-one (12.51 g, 49 mmol, 58% yield) as a dark brown amorphous solid (ca. 80% purity). The material was used in the subsequent step without further purification.

Workup

customThe flask was fitted with a reflux condenser

Sources & evidence

ORD record: ord-456244b3aa8a49e6ad24eb1f56dbaae5
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394297B2

Reaction notes

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