Dimethylformamide → 8-bromo-7-fluoro-3-methyl-3,4-dihydroquinoxalin-2(1H)-one
Reaction equation
[Br:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([NH2:9])[C:3]=1[NH2:10].CN(C=O)C.Br[CH:17]([CH3:23])[C:18](OCC)=[O:19].C([O-])(O)=O.[Na+]>[Cl-].[Na+].O>[Br:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]2[C:3]=1[NH:10][C:18](=[O:19])[CH:17]([CH3:23])[NH:9]2Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 90 °C
Procedure
A 500 mL round-bottomed flask charged with 3-bromo-4-fluorobenzene-1,2-diamine (600c) (18 g, 88 mmol), DMF (100 mL), ethyl 2-bromopropionate (Sigma Aldrich, 11.54 mL, 89 mmol) and NaHCO3 (7.60 g powder, 90 mmol) was heated to 90° C. with a reflux condenser for 30 min, then at 120° C. for 15 h. The reaction mixture was cooled to RT, treated with brine and extracted with EtOAc (2×200 mL), washed with brine (3×) and dried over Na2SO4, filtered and concentrated affording crude 8-bromo-7-fluoro-3-methyl-3,4-dihydroquinoxalin-2(1H)-one (21.75 g, 84 mmol, 96% yield) as an orange-brown viscous oil. The material was used in the subsequent step without further purification. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.67 (s, 1H) 6.78-6.89 (m, 1H) 6.48-6.78 (m, 1H) 6.07-6.35 (m, 1H) 1.25 (d, J=6.46 Hz, 3H). 19F NMR (377 MHz, DMSO-d6) δ ppm −120.49 (1F, s). m/z (ESI, +ve ion) 259.0/261.0 (M+H)+.
Workup
- temperatureThe reaction mixture was cooled to RT
- extractionextracted with EtOAc (2×200 mL)
- washwashed with brine (3×)
- dry with materialdried over Na2SO4
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-2bdf83c5850c4bdd888f86e2da2ee4af
- Source dataset
- uspto-grants-2016_07
- Patent number
- US09394297B2
Reaction notes
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