Bromobenzene → Ethyl 4-(4-bromophenyl)-4-methylpiperidine-1-carboxylate

HRID 2044104Notes

Reaction equation

O[C:2]1([CH3:13])[CH2:7][CH2:6][N:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:4][CH2:3]1.[Br:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.FC(F)(F)S(O)(=O)=O.[OH-].[Na+]>>[Br:14][C:15]1[CH:20]=[CH:19][C:18]([C:2]2([CH3:13])[CH2:7][CH2:6][N:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:4][CH2:3]2)=[CH:17][CH:16]=1

Participants

Reactant 4

HCID 7961Bromobenzene

HCID 14798Sodium Hydroxide

HCID 62406Trifluoromethanesulfonic acid

HCID 55277039Ethyl 4-hydroxy-4-methylpiperidine-1-carboxylate

Product 1

HCID 57489651Ethyl 4-(4-bromophenyl)-4-methylpiperidine-1-carboxylateYield 87.4%

Procedure

A mixture of ethyl 4-hydroxy-4-methylpiperidine-1-carboxylate (2.81 g, 15.01 mmol), bromobenzene (23.56 g, 150 mmol), and trifluoromethanesulfonic acid (22.52 g, 150 mmol) was stirred at room temperature for 3 h. The reaction mixture was poured into ice, basified with 1N NaOH, extracted with methylene chloride twice. The combined organic phases were washed with water and concentrated. The residue was purified by MPLC (ISCO, hexane/ethyl acetate, 80 g silica gel column) to give 4.28 g of product as a slightly yellow oil. LCMS: (M+H)+=326.01, 328.01.

Workup

additionThe reaction mixture was poured into ice
extractionextracted with methylene chloride twice
washThe combined organic phases were washed with water
concentrationconcentrated
customThe residue was purified by MPLC (ISCO, hexane/ethyl acetate, 80 g silica gel column)

Sources & evidence

ORD record: ord-f34bf18a00e648539d748faafb38dc96
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08586751B2

Reaction notes

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