Oxalyl chloride → (E)-1-[4-(4-ethoxy-6-methyl-2-pyridyl)piperazin-1-yl]-4,4,4-trifluoro-but-2-en-1-one
Reaction equation
[F:1][C:2]([F:9])([F:8])/[CH:3]=[CH:4]/[C:5](O)=[O:6].C(Cl)(=O)C(Cl)=O.Cl.[CH2:17]([O:19][C:20]1[CH:25]=[C:24]([CH3:26])[N:23]=[C:22]([N:27]2[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]2)[CH:21]=1)[CH3:18]>ClCCl.CN(C=O)C.C(OCC)(=O)C>[CH2:17]([O:19][C:20]1[CH:25]=[C:24]([CH3:26])[N:23]=[C:22]([N:27]2[CH2:28][CH2:29][N:30]([C:5](=[O:6])/[CH:4]=[CH:3]/[C:2]([F:9])([F:8])[F:1])[CH2:31][CH2:32]2)[CH:21]=1)[CH3:18]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 3
Procedure
(E)-4,4,4-Trifluorobut-2-enoic acid (17 mg, 0.12 mmol) was dissolved in dichloromethane (1 ml), oxalyl chloride (11 μl, 0.12 mmol) was added and the resulting solution was stirred at room temperature for 10 minutes. This solution was added to a solution of 1-(4-ethoxy-6-methyl-2-pyridyl)piperazine hydrochloride (22 mg, 0.086 mmol) and TEA (42 μl, 0.3 mmol) in anhydrous DMF (0.5 ml) and the resulting mixture was stirred at room temperature for one hour. The mixture was diluted with ethyl acetate, washed with sat. sodium bicarbonate solution, brine, dried (magnesium sulfate) and concentrated under reduced pressure. The residue was purified by preparative HPLC (Waters X-Bridge, gradient of water containing 0.1% NH3 and acetonitrile) to yield 12 mg of a solid (0.035 mmol, yield 41%).
Workup
- stirringthe resulting mixture was stirred at room temperature for one hour
- washwashed with sat. sodium bicarbonate solution, brine
- dry with materialdried (magnesium sulfate)
- concentrationconcentrated under reduced pressure
- customThe residue was purified by preparative HPLC (Waters X-Bridge, gradient of water containing 0.1% NH3 and acetonitrile)
Sources & evidence
- ORD record
- ord-d2618898ff9b4635860a96f4e08d4b49
- Source dataset
- uspto-grants-2016_02
- Patent number
- US09260441B2
Reaction notes
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