Potassium Carbonate → cis-1-(4-Bromobenzyl)-3,5-dimethylpiperidine

HRID 1888460Notes

Reaction equation

HRID 1888460 reaction equation
[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6]Br)=[CH:4][CH:3]=1.[CH3:10][C@H:11]1[CH2:16][C@H:15]([CH3:17])[CH2:14][NH:13][CH2:12]1.C(=O)([O-])[O-].[K+].[K+]>C1COCC1>[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][N:13]2[CH2:14][C@H:15]([CH3:17])[CH2:16][C@H:11]([CH3:10])[CH2:12]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 685274-Bromobenzyl bromideHCID 7058087(3S,5S)-3,5-dimethylpiperidine

Product 1

HCID 58266703cis-1-(4-Bromobenzyl)-3,5-dimethylpiperidineYield 35.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A suspension of 4-bromobenzyl bromide (4.0 g, 16.0 mmol), cis, trans-(3,5-dimethylpiperidine) (1.81 g, 16.0 mmol) and potassium carbonate (2.65 g, 19.2 mmol) in THF (160 mL) was heated under reflux for 24 h. The reaction mixture was allowed to cool to ambient temperature, the solid removed by filtration and the filtrate evaporated in vacuo. The resultant residue was loaded onto a 50 g SCX-2 cartridge which was washed with methanol then eluted with 2N ammonia in methanol. Concentration of the combined basic fractions in vacuo followed by flash chromatography of the resultant residue (silica, 330 g column, ISCO, 0-25% ethyl acetate in pentane) afforded cis-1-(4-bromobenzyl)-3,5-dimethylpiperidine (1.60 g, 35%) as a colourless oil. 1H NMR (CDCl3, 300 MHz): 7.47-7.39 (m, 2H); 7.20 (d, J=8.0 Hz, 2H); 3.42 (s, 2H); 2.82-2.71 (m, 2H); 1.76-1.61 (m, 4H); 1.51-1.37 (m, 2H); 0.82 (d, J=6.4 Hz, 6H).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 24 h
  3. customthe solid removed by filtration
  4. customthe filtrate evaporated in vacuo
  5. washwas washed with methanol
  6. washthen eluted with 2N ammonia in methanol

Sources & evidence

ORD record
ord-bac5a03df0c8477a826b5b71cb163ad7
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

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