3-Bromopentane → (3R,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(pentan-3-yl)piperidin-2-one
Reaction equation
[CH2:1]([C@@H:4]1[CH2:9][C@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=2)[C@@H:7]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[NH:6][C:5]1=[O:24])[CH:2]=[CH2:3].Br[CH:26]([CH2:29][CH3:30])[CH2:27][CH3:28].[H-].[Na+]>>[CH2:1]([C@@H:4]1[CH2:9][C@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=2)[C@@H:7]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[N:6]([CH:26]([CH2:29][CH3:30])[CH2:27][CH3:28])[C:5]1=[O:24])[CH:2]=[CH2:3]Participants
Procedure
To a solution of (3R,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)piperidin-2-one (Example 42, Step A) (440 mg, 1.221 mmol) in 3-bromopentane (3196 μL, 25.6 mmol) under nitrogen at rt was added a dispersion of 60% sodium hydride in mineral oil (244 mg, 6.11 mmol). Evolution of gas was observed. The reaction was stirred at room temperature for 10 min and then heated to 120° C. under N2 for 19 h. The reaction mixture was cooled to room temperature and quenched with sat. NH4Cl. The layers were separated and the organic layer was dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (eluent: 0 to 25% EtOAc in hexanes) to give the title compound (375 mg, 71% yield) as a mixture of diastereomers.
Workup
- temperatureheated to 120° C. under N2 for 19 h
- temperatureThe reaction mixture was cooled to room temperature
- customquenched with sat. NH4Cl
- customThe layers were separated
- dry with materialthe organic layer was dried over Na2SO4
- concentrationconcentrated under reduced pressure
- customThe residue was purified by flash chromatography on silica gel (eluent: 0 to 25% EtOAc in hexanes)
Sources & evidence
- ORD record
- ord-22bc53a459004ffaa86ba1890b4f3646
- Source dataset
- uspto-grants-2013_10
- Patent number
- US08569341B2
Reaction notes
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