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

HRID 51263Notes

Reaction equation

HRID 51263 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.O.[H][H]>[Rh].CO>[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 962WaterHCID 1140TolueneHCID 314742(2,3-Dimethoxyphenyl)(4-pyridinyl)methanolHCID 178418361HCID 178418361, compound

Product 1

HCID 10890362(2,3-Dimethoxyphenyl)(piperidin-4-yl)methanol

Reagents, catalysts & solvents 2

HCID 23948RhodiumCatalystHCID 887MethanolSolvent

Procedure

A suitable inert reactor is charged with 4-[1-hydroxy-1-(2,3-dimethoxyphenyl)methyl]pyridine (10) (13.6 kg, 55.5 mol) as a toluene wet cake and 5% rhodium on carbon catalyst (2.7 kg, 50% wet with water) as a water wet cake at about 25° C. About 190 kg of methanol is added and the reactor is pressured to about 100 psig with hydrogen for about 4-12 hours at about 50° C. The catalyst is removed by filtration and the reactor and catalyst are rinsed with about 7 kg of methanol. Deionized water is used as a final wash of the catalyst wet cake. The reactor rinse filtrate and the reaction mixture filtrate are combined. The concentration of 4-[1-hydroxy-1-(2,3-dimethoxyphenyl)methyl]piperidine (11) is about 7 wt %, affording about 13 kg (90% average yield) of the title compound (11).

Workup

  1. customThe catalyst is removed by filtration
  2. washthe reactor and catalyst are rinsed with about 7 kg of methanol
  3. washa final wash of the catalyst wet cake
  4. washThe reactor rinse filtrate
  5. customaffording

Sources & evidence

ORD record
ord-49f67a95f8fe42d4b3b03347ce6c57e7
Source dataset
uspto-grants-2004_03
Patent number
US06713627B2

Reaction notes

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