Piperidine-1-propanol → 2-(3-piperidinopropoxy)-4-(4-{3-[(3S)-3-methylpiperidin-1-yl]propoxy}phenyl)pyridine

HRID 657669Notes

Reaction equation

HRID 657669 reaction equation
[OH:1][CH2:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1.[Na].Cl[C:13]1[CH:18]=[C:17]([C:19]2[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH2:27][CH2:28][N:29]3[CH2:34][CH2:33][CH2:32][C@H:31]([CH3:35])[CH2:30]3)=[CH:21][CH:20]=2)[CH:16]=[CH:15][N:14]=1>ClCCl>[N:5]1([CH2:4][CH2:3][CH2:2][O:1][C:15]2[CH:16]=[C:17]([C:19]3[CH:20]=[CH:21][C:22]([O:25][CH2:26][CH2:27][CH2:28][N:29]4[CH2:34][CH2:33][CH2:32][C@H:31]([CH3:35])[CH2:30]4)=[CH:23][CH:24]=3)[CH:18]=[CH:13][N:14]=2)[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1

Participants

5

Reactant 3

HCID 66032Piperidine-1-propanolHCID 5360545SodiumHCID 576720232-chloro-4-(4-{3-[(3S)-3-methylpiperidin-1-yl]propoxy}phenyl)pyridine

Product 1

HCID 159410712-(3-piperidinopropoxy)-4-(4-{3-[(3S)-3-methylpiperidin-1-yl]propoxy}phenyl)pyridineYield 15.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 1-(3-hydroxypropyl)piperidine (287 mg) are successively added sodium (46 mg) and 2-chloro-4-(4-{3-[(3S)-3-methylpiperidin-1-yl]propoxy}phenyl)pyridine (345 mg). The mixture is heated overnight, cooled back to room temperature and dissolved in dichloromethane (20 mL). The organic phase is washed with water (20 mL), dried over magnesium sulphate, concentrated under reduced pressure and purified over silica gel (eluent (dichloromethane/methanol from 100/0 to 90/10). Fraction containing the expected product are pooled and concentrated under reduced pressure. The crude base is dissolved in ethanol, oxalic acid (32 mg) is added and the precipitate that appears separated by filtration and dried to give 70 mg of 2-(3-piperidinopropoxy)-4-(4-{3-[(3S)-3-methylpiperidin-1-yl]propoxy}phenyl)pyridine, dioxalate as a white solid melting at 122° C.

Workup

  1. temperatureThe mixture is heated overnight
  2. washThe organic phase is washed with water (20 mL)
  3. dry with materialdried over magnesium sulphate
  4. concentrationconcentrated under reduced pressure
  5. custompurified over silica gel (eluent (dichloromethane/methanol from 100/0 to 90/10)
  6. additionFraction containing the expected product
  7. concentrationconcentrated under reduced pressure
  8. dissolutionThe crude base is dissolved in ethanol
  9. additionoxalic acid (32 mg) is added
  10. customthe precipitate that appears separated by filtration
  11. customdried

Sources & evidence

ORD record
ord-7e865a1bf51a45729139e7c4b083677f
Source dataset
uspto-grants-2011_12
Patent number
US08076329B2

Reaction notes

Loading…