Phosphorus oxychloride → 3,5-Dichloro-2-ethylquinoxaline
Reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[NH:10][C:9](=O)[C:8]([CH2:13][CH3:14])=[N:7]2.O=P(Cl)(Cl)[Cl:17]>>[Cl:17][C:9]1[C:8]([CH2:13][CH3:14])=[N:7][C:6]2[C:11]([N:10]=1)=[C:2]([Cl:1])[CH:3]=[CH:4][CH:5]=2Participants
Procedure
A thick slurry of 8-chloro-3-ethylquinoxalin-2(1H)-one (1.00 Kg, 4.79 mol) in POCl3 (2.68 L, 28.8 mol) was stirred at 100° C. for 2 h. At this time LC-MS analysis showed that the reaction was complete. After the removal of most of the POCl3 under reduced pressure, the residue was poured carefully into ice-water and neutralized with a combination of 2M aq. NaOH and saturated aq. NaHCO3. The resulting suspension was extracted with DCM (3×4 L). The organic phase was washed with brine, dried over anhydrous Na2SO4, filtered, and evaporated under reduced pressure. The crude was purified by flash column chromatography eluting with hexane/EtOAc (30/1) to give 3,5-dichloro-2-ethylquinoxaline (840 g) as a white solid. 1H NMR (DMSO-d6) δ ppm 8.01-8.08 (m, 2H), 7.84 (t, J=8.0 Hz, 1H), 3.10-3.17 (d, J=7.3 Hz, 2H), 1.36 (t, J=7.3 Hz, 3H). Mass Spectrum (ESI) m/z=227.1 (M+1).
Workup
- customAfter the removal of most of the POCl3 under reduced pressure
- additionthe residue was poured carefully into ice-water
- extractionThe resulting suspension was extracted with DCM (3×4 L)
- washThe organic phase was washed with brine
- dry with materialdried over anhydrous Na2SO4
- filtrationfiltered
- customevaporated under reduced pressure
- customThe crude was purified by flash column chromatography
- washeluting with hexane/EtOAc (30/1)
Sources & evidence
- ORD record
- ord-a70d8cb72b914c408c956c122fe403d9
- Source dataset
- uspto-grants-2014_09
- Patent number
- US08835432B2
Reaction notes
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