Piperidine → 1-(4-Methoxy-2-trifluoromethyl-phenyl)-piperidine
Reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[C:10]([F:13])([F:12])[F:11].[NH:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1.[Cl-].C(C1C=CC=C(C(C)C)C=1C1NC=C[N+]=1C1C(C(C)C)=CC=CC=1C(C)C)(C)C>O1CCOCC1.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]>[CH3:9][O:8][C:5]1[CH:6]=[CH:7][C:2]([N:14]2[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]2)=[C:3]([C:10]([F:13])([F:12])[F:11])[CH:4]=1Participants
6
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 150 °C
Procedure
To a solution of 1-Bromo-4-methoxy-2-trifluoromethyl-benzene (500 mg, 1.961 mmol) in 1,4-dioxane (8 mL) is added sequentially: piperidine (2 eq., 3.921 mmol, 0.41 mL), Pd2dba3 (2 mol %, 0.039 mmol, 36 mg), KtOBu (1.5 eq., 2.941 mmol, 330 mg) and 1,3-(Bis(2,6-di-iso-propylphenyl)-imidazolium chloride (iPrHCl, 4 mol %, 0.078 mmol, 33 mg). The resulting reaction mixture is heated in a sealed tube at 150° C. oil bath for 12 hours. After cooling to room temperature, the reaction mixture is concentrated. The residue obtained is partially purified by silica gel chromatography (9:1 hexanes/EtOAc) to give crude 1-(4-Methoxy-2-trifluoromethyl-phenyl)-piperidine.
Workup
- customThe resulting reaction mixture
- temperatureAfter cooling to room temperature
- concentrationthe reaction mixture is concentrated
- customThe residue obtained
- customis partially purified by silica gel chromatography (9:1 hexanes/EtOAc)
Sources & evidence
- ORD record
- ord-ce421a24f2e64bda846ad57a65d0b82f
- Source dataset
- uspto-grants-2009_08
- Patent number
- US07572811B2
Reaction notes
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