Methyl 1-Benzyl-1,2,3,6-tetrahydropyridine-4-carboxylate → Methyl 1-benzyl-3-(3-bromo5-methyl-phenyl)piperidine-4-carboxylate

HRID 1714140Notes

Reaction equation

C1COCC1.C1(C)C=CC=CC=1.[Br:13][C:14]1[CH:15]=[C:16]([Mg]Br)[CH:17]=[C:18]([CH3:20])[CH:19]=1.[CH2:23]([N:30]1[CH2:35][CH:34]=[C:33]([C:36]([O:38][CH3:39])=[O:37])[CH2:32][CH2:31]1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>C1C=CC=CC=1>[CH2:23]([N:30]1[CH2:31][CH2:32][CH:33]([C:36]([O:38][CH3:39])=[O:37])[CH:34]([C:16]2[CH:17]=[C:18]([CH3:20])[CH:19]=[C:14]([Br:13])[CH:15]=2)[CH2:35]1)[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

Conditions

Temperature: -15 °C

Procedure

A 2.5 M THF/toluene solution of (3-bromo-5-methylphenyl)magnesium bromide (40 mL, 99 mmol) was cooled to −15° C., and methyl 1-benzyl-1,2,3,6-tetrahydropyridine-4-carboxylate (9.85 g, 42.6 mmol) in benzene (17.5 mL) was slowly added for 3 h at −15° C. The reaction mixture was stirred additional 2 h at −15° C. and warmed to 20° C. The reaction was quenched by addition of saturated NH4Cl aqueous solution followed by extraction with EtOAc. The combined organic solution was dried over MgSO4, filtered and concentrated in vacuo. The residue was chromatographed in silica gel column (Hex/EtOAc 9/1) to give methyl 1-benzyl-3-(3-bromo5-methyl-phenyl)piperidine-4-carboxylate (12.2 g, 30.3 mmol).

Workup

temperaturewarmed to 20° C
customThe reaction was quenched by addition of saturated NH4Cl aqueous solution
extractionfollowed by extraction with EtOAc
dry with materialThe combined organic solution was dried over MgSO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was chromatographed in silica gel column (Hex/EtOAc 9/1)

Sources & evidence

ORD record: ord-bcede513a1d44b43b9027d3e1b14246d
Source dataset: uspto-grants-2010_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07795436B2

Reaction notes

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