Dimethylformamide → 4-[1-Benzyl-4-(3-methoxy-phenyl)-piperidin-4-yl]-benzonitrile

HRID 2085460Notes

Reaction equation

[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([C:22]2[CH:27]=[CH:26][C:25](OS(C(F)(F)F)(=O)=O)=[CH:24][CH:23]=2)([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH3:21])[CH:15]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:36][N:37](C=O)C>C(OCC)C.[C-]#N.[Zn+2].[C-]#N>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([C:22]2[CH:27]=[CH:26][C:25]([C:36]#[N:37])=[CH:24][CH:23]=2)([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH3:21])[CH:15]=2)[CH2:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution of trifluoro-methanesulfonic acid 4-[1-benzyl-4-(3-methoxy-phenyl)-piperidin-4-yl]-phenyl ester (2.2 g, 4.34 mmol) in DMF (8 mL) was added zinc cyanide (0.61 g, 5.22 mmol) and tetrakis triphenylphosphine palladium (0.7 g, 0.63 mmol). The reaction was stirred under a nitrogen atmosphere at 90° C. for 5 hours. The mixture was cooled to room temperature and it was diluted with diethyl ether (100 mL). The organic layer was washed with brine (5×10 mL), dried (MgSO4) and concentrated. Purification with hexanes/EtOAc (2:1) afforded 1.52 g (92% yield) of 4-[1-Benzyl-4-(3-methoxy-phenyl)-piperidin-4-yl]-benzonitrile. 1HNMR (400 MHz, CDCl3) δ 7.51 (d, 2H), 7.34 (d, 2H), 7.28-7.18 (comp, 6H), 6.80 (d, 1H), 6.77 (s, 1H), 6.70(d, 1H), 3.75 (s, 3H), 3.39 (s, 2H), 2.63-2.39 (comp, 8H); MS (M+1) 383.2.

Workup

temperatureThe mixture was cooled to room temperature
washThe organic layer was washed with brine (5×10 mL)
dry with materialdried (MgSO4)
concentrationconcentrated
customPurification with hexanes/EtOAc (2:1)

Sources & evidence

ORD record: ord-c5c4f273b6c0477fa963dad9433fc13f
Source dataset: uspto-grants-2004_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06720336B2

Reaction notes

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