1-Bromopropane → (3R,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-propylpiperidin-2-one

HRID 1048232Notes

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].[H-].[Na+].Br[CH2:28][CH2:29][CH3:30]>CN(C=O)C>[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]([CH2:28][CH2:29][CH3:30])[C:5]1=[O:24])[CH:2]=[CH2:3]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of (3R,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)piperidin-2-one (Example 42, Step A) (70 mg, 0.19 mmol) in 430 μL of DMF was added sodium hydride (60% suspension in mineral oil, 20 mg, 0.51 mmol) at 0° C. The reaction was stirred at 0° C. for 15 min and then treated with 1-bromopropane (53 μL, 0.58 mmol). After being stirred at 25° C. for 4 h, the reaction was quenched with sat. aqueous NaHCO3 and extracted (2×EtOAc). The combined organic layers were washed with sat. aq. NaCl and NaHCO3-solutions, dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. Purification of the residue by silica gel prep plate (25% EtOAc/hexanes) provided the title compound as a colorless solid.

Workup

stirringAfter being stirred at 25° C. for 4 h
customthe reaction was quenched with sat. aqueous NaHCO3
extractionextracted (2×EtOAc)
washThe combined organic layers were washed with sat. aq. NaCl and NaHCO3-solutions
dry with materialdried over Na2SO4
filtrationfiltered
concentrationthe filtrate was concentrated under reduced pressure
customPurification of the residue by silica gel prep plate (25% EtOAc/hexanes)

Sources & evidence

ORD record: ord-e7ac06ec64644bff8003829016c43567
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08569341B2

Reaction notes

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