Potassium Carbonate → HCID 86679691, compound

HRID 2367672Notes

Reaction equation

HRID 2367672 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH2:8]Cl)[CH:7]=1.[CH3:10][C@H:11]1[CH2:16][CH2:15][CH2:14][C@@H:13]([CH3:17])[NH:12]1.C([O-])([O-])=O.[K+].[K+]>CC#N>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH2:8][N:12]2[C@@H:13]([CH3:17])[CH2:14][CH2:15][CH2:16][C@H:11]2[CH3:10])[CH:7]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 641768rel-(2R,6S)-2,6-Dimethylpiperidine2×HCID 117012593-Bromo-5-(chloromethyl)pyridine

Product 1

HCID 86679691HCID 86679691, compoundYield 53.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 3-bromo-5-(chloromethyl)pyridine (XLVI) (1.17 g, 4.8 mmol) in MeCN (0.2 mL) and (2S,6R)-2,6-dimethylpiperidine (2.6 mL, 19.3 mmol) was added K2CO3 (667 mg, 4.8 mmol). The reaction was refluxed for 5 hrs. TLC showed the presence of starting material so additional (2S,6R)-2,6-dimethylpiperidine (2.0 mL, 14.8 mmol) was added and the reaction was refluxed for an additional 5 hrs. The solvent was removed and the residue was partitioned between EtOAc/water. The EtOAc was separated and washed with brine, dried over MgSO4 and concentrated under vacuum. The residue was purified on a silica gel column (100% hexanes→6:94 EtOAc:hexanes) to afford 3-bromo-5-(((2R,6S)-2,6-dimethylpiperidin-1-yl)methyl)pyridine (XLVII) as a clear oil (728 mg, 2.57 mmol, 53% yield). 1H NMR (DMSO-d6) δ ppm 0.92 (d, J=8 Hz, 6H), 1.21-1.32 (m, 3H), 1.52-1.55 (m, 2H), 1.59-1.63 (m, 1H), 2.42-2.46 (m, 2H), 3.73 (s, 2H), 7.97-7.98 (m, 1H), 8.50 (d, J=3 Hz, 1H), 8.55-8.56 (m, 1H); ESIMS found for C13H19BrN2 m/z 283 (M+H).

Workup

  1. temperatureThe reaction was refluxed for 5 hrs
  2. additionwas added
  3. temperaturethe reaction was refluxed for an additional 5 hrs
  4. customThe solvent was removed
  5. customthe residue was partitioned between EtOAc/water
  6. customThe EtOAc was separated
  7. washwashed with brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated under vacuum
  10. customThe residue was purified on a silica gel column (100% hexanes→6:94 EtOAc:hexanes)

Sources & evidence

ORD record
ord-cfca765aaa59420fa0e1724b89de63b6
Source dataset
uspto-grants-2014_04
Patent number
US08697887B2

Reaction notes

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