Sodium Iodide → (R)-2-hydroxymethyl-1-(4-methoxyphenethyl)piperidine

HRID 1859420Notes

Reaction equation

HRID 1859420 reaction equation
[OH:1][CH2:2][C@H:3]1[CH2:8][CH2:7][CH2:6][CH2:5][NH:4]1.S(C1C=CC(C)=CC=1)(O[CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=1)(=O)=O.C(=O)([O-])[O-].[Na+].[Na+].[I-].[Na+]>C(#N)C>[OH:1][CH2:2][C@H:3]1[CH2:8][CH2:7][CH2:6][CH2:5][N:4]1[CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 10340Sodium CarbonateHCID 2853842-(4-Methoxyphenyl)ethyl 4-methylbenzenesulfonateHCID 6950192(2R)-piperidin-2-ylmethanol

Product 1

HCID 69902512(R)-2-hydroxymethyl-1-(4-methoxyphenethyl)piperidine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

(R)-2-hydroxymethylpiperidine [prepared by a process described in Japanese Patent Unexamined Published Application (hereinafter referred to as “J. P. KOKAI”) No. Sho 48-19597] (600 mg, 5.22 mmol), 4-methoxyphenethyl tosylate (1.76 g, 5.74 mmol), sodium carbonate (608 mg, 5.74 mmol) and sodium iodide (100 mg, 0.67 mmol) were added to acetonitrile (50 ml), and they were heated under reflux at 90° C. for 3.5 hours. The solvent was evaporated under reduced pressure. The residue was distributed in ethyl acetate and saturated aqueous sodium hydrogencarbonate solution. The organic layer was washed with water and dried over magnesium sulfate. Then the solvent was evaporated under reduced pressure. The obtained residue was subjected to silica gel column chromatography. The product was eluted with hexane and dichloromethane (1:1), then with dichloromethane and finally with dichloromethane and methanol (20:1). The appropriate fractions were combined, and the solvent was evaporated under reduced pressure to obtain (R)-2-hydroxymethyl-1-(4-methoxyphenethyl)piperidine in the form of a light yellow oil (617 mg, 47%).

Workup

  1. temperaturewere heated
  2. customThe solvent was evaporated under reduced pressure
  3. washThe organic layer was washed with water
  4. dry with materialdried over magnesium sulfate
  5. customThen the solvent was evaporated under reduced pressure
  6. washThe product was eluted with hexane and dichloromethane (1:1)
  7. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-52b87756a3984ef091d9ee67f48e29f4
Source dataset
uspto-grants-2003_03
Patent number
US06528504B2

Reaction notes

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