4-Phenylpiperidine → 2,3-Dichloro-4-(4-phenyl-1-piperidinyl)pyridine

HRID 587632Notes

Reaction equation

HRID 587632 reaction equation
[Cl:1][C:2]1[C:7]([Cl:8])=[C:6](I)[CH:5]=[CH:4][N:3]=1.[C:10]1([CH:16]2[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.CCN(C(C)C)C(C)C.C([O-])(O)=O.[Na+]>CC#N>[Cl:1][C:2]1[C:7]([Cl:8])=[C:6]([N:19]2[CH2:20][CH2:21][CH:16]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[CH2:17][CH2:18]2)[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 698734-PhenylpiperidineHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 448870382,3-Dichloro-4-iodopyridine

Product 1

HCID 574595972,3-Dichloro-4-(4-phenyl-1-piperidinyl)pyridine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of D10 (4 g, 14.605 mmol), 4-phenylpiperidine (3.532 g, 21.907 mmol) and DIPEA (5.088 ml, 29.209 mmol) in CH3CN (150 ml) was heated in a sealed tube at 110° C. for 16 h. The mixture was then treated with NaHCO3 (aqueous sat. solution). The resulting mixture was extracted with EtOAc. The organic layer was separated, dried (Na2SO4) and concentrated in vacuo. The crude product was purified by column chromatography (silica gel; DCM/7M solution of NH3 in MeOH/EtOAc gradient as eluent). The desired fractions were collected and concentrated in vacuo to yield intermediate compound D14 (2.32 g, 52%) as a white solid.

Workup

  1. extractionThe resulting mixture was extracted with EtOAc
  2. customThe organic layer was separated
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by column chromatography (silica gel; DCM/7M solution of NH3 in MeOH/EtOAc gradient as eluent)
  6. customThe desired fractions were collected
  7. concentrationconcentrated in vacuo
  8. customto yield intermediate compound D14 (2.32 g, 52%) as a white solid

Sources & evidence

ORD record
ord-a6872e7637da46149d7ee195ad3f539e
Source dataset
uspto-grants-2016_01
Patent number
US09226930B2

Reaction notes

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