1-Methylpiperazine → N-[2-trifluoromethoxy-5-(4-methyl-piperazin-1-yl)-phenyl]-acetamide
Reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([O:12][C:13]([F:16])([F:15])[F:14])=[C:6]([NH:8][C:9](=[O:11])[CH3:10])[CH:7]=1.[Li]N([Si](C)(C)C)[Si](C)(C)C.[CH3:27][N:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1>[CH3:27][N:28]1[CH2:33][CH2:32][N:31]([C:2]2[CH:3]=[CH:4][C:5]([O:12][C:13]([F:16])([F:15])[F:14])=[C:6]([NH:8][C:9](=[O:11])[CH3:10])[CH:7]=2)[CH2:30][CH2:29]1Participants
6
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Procedure
Pd2(dba)3 (155 mg, 0.17 mmol), 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)-biphenyl (133 mg, 0.34 mmol), N-(5-bromo-2-trifluoromethoxy-phenyl)-acetamide (5.05 g, 17 mmol)) were charged in a round-bottom flask flushed with argon. The flask was evacuated and backfilled with argon. LiN(TMS)2 solution (1M in THF, 37.6 mL) and N-methylpiperazine (2.3 mL, 20.5 mmol) were added and the reaction mixture refluxed for 3 h. The reaction mixture was then allowed to cool to room temperature and concentrated. The crude solid was purified by flash chromatography on silica gel (eluant: DCM/EtOH 90/10) to afford 4.78 g (88% yield) of the N-[5-(4-methyl-piperazin-1-yl)-2-trifluoromethoxy-phenyl]-acetamide.
Workup
- customflushed with argon
- customThe flask was evacuated
- temperaturethe reaction mixture refluxed for 3 h
- concentrationconcentrated
- customThe crude solid was purified by flash chromatography on silica gel (eluant: DCM/EtOH 90/10)
Sources & evidence
- ORD record
- ord-f3d68f6b73924422a3348f7d2ccba641
- Source dataset
- uspto-grants-2013_12
- Patent number
- US08614220B2
Reaction notes
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