Potassium Carbonate → 2-chloro-4-(4-{3-[(3S)-3-methylpiperidin-1-yl]propoxy}phenyl)pyridine

HRID 657666Notes

Reaction equation

HRID 657666 reaction equation
Br.[Cl:2][C:3]1[CH:8]=[C:7]([C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=2)[CH:6]=[CH:5][N:4]=1.C(=O)([O-])[O-].[K+].[K+].Cl.CS(O[CH2:28][CH2:29][CH2:30][N:31]1[CH2:36][CH2:35][CH2:34][C@H:33]([CH3:37])[CH2:32]1)(=O)=O>CN(C)C=O>[Cl:2][C:3]1[CH:8]=[C:7]([C:9]2[CH:10]=[CH:11][C:12]([O:15][CH2:28][CH2:29][CH2:30][N:31]3[CH2:36][CH2:35][CH2:34][C@H:33]([CH3:37])[CH2:32]3)=[CH:13][CH:14]=2)[CH:6]=[CH:5][N:4]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 86629975(3S)-1-(3-methane-sulfonyloxypropyl)-3-methylpiperidine hydrochlorideHCID 1363359722-Chloro-4-(4-hydroxyphenyl)pyridine hydrobromide

Product 1

HCID 576720232-chloro-4-(4-{3-[(3S)-3-methylpiperidin-1-yl]propoxy}phenyl)pyridine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A To a mixture of 2-chloro-4-(4-hydroxyphenyl)pyridine hydrobromide (593 m g) and potassium carbonate (1.66 g) in N,N-dimethylformamide (15 mL) heated at a temperature close to 65° C. is added (3S)-1-(3-methane-sulfonyloxypropyl)-3-methylpiperidine hydrochloride (625 mg). The mixture is heated at a temperature close to 65° C. for six hours, allowed to cool back to room temperature and filtered. The precipitate is washed with N,N-dimethylformamide and the organic phases are concentrated under reduced pressure. The residue is purified by column chromatography over silica gel (eluent dichloromethane/methanol from 100/0 to 90/10) to afford 434 mg of 2-chloro-4-(4-{3-[(3S)-3-methylpiperidin-1-yl]propoxy}phenyl)pyridine as an orange oil. Conversion to the oxalate is performed by mixing the crude base (87 mg) and oxalic acid (46 mg) in a mixture of ethanol and diethyl ether. Filtration of the insoluble and drying under reduced pressure gives 82 mg of 2-chloro-4-(4-{3-[(3S)-3-methylpiperidin-1-yl]propoxy}phenyl)pyridine, dioxalate as an off white solid melting at 143° C.

Workup

  1. temperatureheated at a temperature
  2. customclose to 65° C.
  3. temperatureThe mixture is heated at a temperature
  4. customclose to 65° C. for six hours
  5. filtrationfiltered
  6. washThe precipitate is washed with N,N-dimethylformamide
  7. concentrationthe organic phases are concentrated under reduced pressure
  8. customThe residue is purified by column chromatography over silica gel (eluent dichloromethane/methanol from 100/0 to 90/10)

Sources & evidence

ORD record
ord-b655489ea6d9444e97ffabfbb4178ae6
Source dataset
uspto-grants-2011_12
Patent number
US08076329B2

Reaction notes

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