Sodium hydride → 1-(4-(Benzyloxy)benzyl)-6-(2,6-dimethoxyphenyl)piperidin-2-one

HRID 594367Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[C:4]=1[CH:11]1[NH:16][C:15](=[O:17])[CH2:14][CH2:13][CH2:12]1.[H-].[Na+].[CH2:20]([O:27][C:28]1[CH:33]=[CH:32][C:31]([CH2:34]Cl)=[CH:30][CH:29]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C([O-])(O)=O.[Na+]>CN(C=O)C>[CH2:20]([O:27][C:28]1[CH:29]=[CH:30][C:31]([CH2:34][N:16]2[CH:11]([C:4]3[C:5]([O:9][CH3:10])=[CH:6][CH:7]=[CH:8][C:3]=3[O:2][CH3:1])[CH2:12][CH2:13][CH2:14][C:15]2=[O:17])=[CH:32][CH:33]=1)[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of 6-(2,6-dimethoxyphenyl)piperidin-2-one (110 mg; 0.46 mmol) in anh. DMF (2 ml) was treated at rt with NaH (60% dispersion in mineral oil; 118 mg; 2.95 mmol), and with commercially available 1-(benzyloxy)-4-(chloromethyl)benzene (130 mg; 0.56 mmol). The resulting mixture was then heated to 60° C., under nitrogen, for 1 h. After cooling to rt, aq. sat. NaHCO3 was added, and this mixture was extracted with AcOEt (2×). The mixed organic layers were washed with brine, dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by FC (AcOEt) afforded 1-(4-(benzyloxy)benzyl)-6-(2,6-dimethoxyphenyl)piperidin-2-one as a yellow oil. LC-MS (conditions E): tR=0.82 min.; [M+H]+: 432.24 g/mol.

Workup

temperatureAfter cooling to rt
extractionthis mixture was extracted with AcOEt (2×)
washThe mixed organic layers were washed with brine
dry with materialdried over anh. MgSO4
filtrationfiltered
concentrationconcentrated to dryness under reduced pressure
customPurification by FC (AcOEt)

Sources & evidence

ORD record: ord-dea0a18cd1da44a383ae113ef79cd7e9
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09242970B2

Reaction notes

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