Cesium carbonate → Tert-butyl 4-(6-chloropyrazin-2-YL)piperazine-1-carboxylate
Reaction equation
Cl[C:2]1[CH:7]=[N:6][CH:5]=[C:4]([Cl:8])[N:3]=1.[N:9]1([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1.C(=O)([O-])[O-].[Cs+].[Cs+]>>[Cl:8][C:4]1[N:3]=[C:2]([N:12]2[CH2:11][CH2:10][N:9]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:14][CH2:13]2)[CH:7]=[N:6][CH:5]=1Participants
Conditions
- Temperature
- 100 °C
Procedure
2,6-dichloropyrazine (10.0 g, 67.1 mmol), tert-butyl piperazine-1-carboxylate (12.5 g, 67.1 mmol) and cesium carbonate (43.7 g, 134 mmol) were added to a round bottom flask and flushed with nitrogen. DMF (300 ml) was then added and the reaction was stirred at 100° C. for 3 hours. The reaction mixture was cooled to room temperature, then diluted with EtOAc (600 mL) and washed with brine (600 mL). The aqueous layer was washed with additional EtOAc (600 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated to a crude residue that was purified by silica gel chromatography to afford tert-butyl 4-(6-chloropyrazin-2-yl)piperazine-1-carboxylate as an off-white solid. LRMS calculated for C13H19ClN4O2[M+H]+, 299.1; found 299.1.
Workup
- customflushed with nitrogen
- additionDMF (300 ml) was then added
- temperatureThe reaction mixture was cooled to room temperature
- additiondiluted with EtOAc (600 mL)
- washwashed with brine (600 mL)
- washThe aqueous layer was washed with additional EtOAc (600 mL)
- dry with materialThe combined organic layers were dried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated to a crude residue that
- customwas purified by silica gel chromatography
Sources & evidence
- ORD record
- ord-9131105400ca417a9b66209565f40e63
- Source dataset
- uspto-grants-2012_05
- Patent number
- US08183245B2
Reaction notes
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