Cesium carbonate → 4-[1-(4-Trifluoromethyl-phenyl)-piperidin-4-yl]-butyric acid methyl ester
Reaction equation
C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl.[CH3:54][O:55][C:56](=[O:66])[CH2:57][CH2:58][CH2:59][CH:60]1[CH2:65][CH2:64][NH:63][CH2:62][CH2:61]1.Br[C:68]1[CH:73]=[CH:72][C:71]([C:74]([F:77])([F:76])[F:75])=[CH:70][CH:69]=1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:54][O:55][C:56](=[O:66])[CH2:57][CH2:58][CH2:59][CH:60]1[CH2:65][CH2:64][N:63]([C:68]2[CH:73]=[CH:72][C:71]([C:74]([F:77])([F:76])[F:75])=[CH:70][CH:69]=2)[CH2:62][CH2:61]1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
A mixture of palladium (II) acetate (42 mg; 0.185 mmol), (±)-2,2′-bis-diphenylphosphanyl-[1,1′]binaphthalenyl (170 mg; 0.275 mmol), cesium carbonate (867 g; 2.66 mmol) in dioxane (5 mL) is placed in an ultrasonic bath for 30 minutes. 4-Piperidin-4-yl-butyric acid methyl ester hydrochloride (290 mg; 1.33 mmol, prepared in accordance with Example 131) and 1-bromo-4-trifluoromethyl-benzene (299 mg; 1.33 mmol) are then added and the reaction mixture is stirred for 2 hours under reflux. After dilution with ethyl acetate, the mixture is filtered and the filtrate concentrated under high vacuum. The obtained residue is purified by column chromatography on silica gel (hexanes/dichloromethane 50:50 v/v to 100) to afford the desired compound (284 mg; 0.86 mmol).
Workup
- temperatureunder reflux
- filtrationAfter dilution with ethyl acetate, the mixture is filtered
- concentrationthe filtrate concentrated under high vacuum
- customThe obtained residue is purified by column chromatography on silica gel (hexanes/dichloromethane 50:50 v/v to 100)
Sources & evidence
- ORD record
- ord-a3fa80e85c514e58933896c8e38f084c
- Source dataset
- uspto-grants-2015_08
- Patent number
- US09096524B2
Reaction notes
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