1-Methylpiperazine → 1,1-Dimethylethyl 3-[4-(4-methyl-1-piperazinyl)phenyl]-1-piperidinecarboxylate

HRID 1784708Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([C:14]2[CH:19]=[CH:18][C:17](Br)=[CH:16][CH:15]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.CC(C)([O-])C.[Na+].[CH3:48][N:49]1[CH2:54][CH2:53][NH:52][CH2:51][CH2:50]1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([C:14]2[CH:19]=[CH:18][C:17]([N:52]3[CH2:53][CH2:54][N:49]([CH3:48])[CH2:50][CH2:51]3)=[CH:16][CH:15]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 90 °C

Procedure

To a suspension of 3-(4-bromophenyl)-piperidine-1-carboxylic acid tert-butyl ester (3.0 g, 8.8 mmol), palladium acetate (80 mg, 0.36 mmol), 2-(di-t-butyl phosphino)biphenyl (210 mg, 0.70 mmol), and sodium t-butoxide (1.2 g, 125 mmol) in toluene (30 mL) was added N-methylpiperazine (1.3 g, 13.0 mmol) at room temperature. After heating at 90° C. for 5 h, the resulting suspension was passed through a Celite column. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel chromatography eluting 5-25% of ethyl acetate in hexane to afford 3-(4-(4-methylpiperazin-1-yl)-phenyl)-piperidine-1-carboxylic acid tert-butyl ester (2.0 g, 5.56 mmol, 63%) as white crystals.

Workup

concentrationThe filtrate was concentrated under reduced pressure
customthe residue was purified by silica gel chromatography
washeluting 5-25% of ethyl acetate in hexane

Sources & evidence

ORD record: ord-63f98dd0911049c8ac37e68b334e3a3e
Source dataset: uspto-grants-2009_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07504411B2

Reaction notes

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