Sodium hydride → 1-([1,1'-Biphenyl]-3-ylmethyl)-6-(2,6-dimethoxyphenyl)piperidin-2-one

HRID 594389Notes

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+].Br[CH2:21][C:22]1[CH:23]=[C:24]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:25]=[CH:26][CH:27]=1.C([O-])(O)=O.[Na+]>CN(C=O)C>[C:24]1([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:25]=[CH:26][CH:27]=[C:22]([CH2:21][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:23]=1

Participants

Conditions

Temperature: 60 °C

Procedure

A solution of 6-(2,6-dimethoxyphenyl)piperidin-2-one (70 mg; 0.29 mmol; 1.0 equiv.) in anh. DMF (3 ml) was treated at rt with NaH (60% dispersion in mineral oil; 71 mg; 1.78 mmol; 6.0 equiv.), and 3-(bromomethyl)-1,1′-biphenyl (110 mg; 0.44 mmol; 1.5 equiv.). The resulting mixture was then heated to 60° C., under nitrogen, for 1 h. The reaction mixture was allowed to cool to rt, and a solution of aq. sat. NaHCO3 (10 ml) was added. After extractions with AcOEt (2×20 ml), the mixed organic layers were further washed with brine (10 ml), dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by preparative HPLC afforded 1-([1,1′-biphenyl]-3-ylmethyl)-6-(2,6-dimethoxyphenyl)piperidin-2-one as a colorless oil. LC-MS (conditions A): tR=0.95 min.; [M+H]+: 402.16 g/mol.

Workup

temperatureto cool to rt
extractionAfter extractions with AcOEt (2×20 ml)
washthe mixed organic layers were further washed with brine (10 ml)
dry with materialdried over anh. MgSO4
filtrationfiltered
concentrationconcentrated to dryness under reduced pressure
customPurification by preparative HPLC

Sources & evidence

ORD record: ord-a14b6773a2334ed98c7a14a93ca6b90f
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09242970B2

Reaction notes

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