Methanol → (2,3-Dimethoxyphenyl)(piperidin-4-yl)methanol

HRID 51264Notes

Reaction equation

HRID 51264 reaction equation
[OH:1][CH:2]([C:13]1[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[C:4]=1[O:11][CH3:12].C1(C)C=CC=CC=1.CO.[H][H]>[Rh].C(O)(=O)C>[OH:1][CH:2]([CH:13]1[CH2:14][CH2:15][NH:16][CH2:17][CH2:18]1)[C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[C:4]=1[O:11][CH3:12]

Participants

7

Reactant 4

HCID 887MethanolHCID 1140TolueneHCID 314742(2,3-Dimethoxyphenyl)(4-pyridinyl)methanolHCID 178418361HCID 178418361, compound

Product 1

HCID 10890362(2,3-Dimethoxyphenyl)(piperidin-4-yl)methanolYield 96%

Reagents, catalysts & solvents 2

HCID 23948RhodiumCatalystHCID 176Acetic AcidSolvent

Procedure

Into a suitable inerted reactor was charged 118 kg (481 mol) of 4-[1-hydroxy-1-(2,3-dimethoxyphenyl)methyl]pyridine (10) as a toluene wet cake and 23.6 kg of 5% rhodium on carbon catalyst at 25° C. To the slurry was then added 850 kg of methanol and 29 kg of glacial acetic acid. The reactor was then pressurized to about 100 psi with hydrogen for about 4-12 hours1 at 40° C. The catalyst was removed by filtration and the reactor and the catalyst were rinsed with 150 kg of methanol.2 The reactor rinse filtrate and the reaction mixture filtrate were combined. The concentration of 4-[1-hydroxy-1-(2,3-dimethoxyphenyl)methyl]piperidine (11) is typically about 10 wt %, affording about 116 kg of 4-[1-hydroxy-1-(2,3-dimethoxyphenyl)methyl]piperidine (11) (96% yield)3.

Workup

  1. customThe catalyst was removed by filtration
  2. washthe reactor and the catalyst were rinsed with 150 kg of methanol
  3. wash2 The reactor rinse filtrate

Sources & evidence

ORD record
ord-618235ac678c43d9af7c7634e866b26b
Source dataset
uspto-grants-2004_03
Patent number
US06713627B2

Reaction notes

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