Methanol → (2,3-Dimethoxyphenyl)(piperidin-4-yl)methanol
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
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. 1A HPLC analysis of the reaction mixture is used to determine that the reaction conversion is at least 98%.2For increase safety, deionized water may be used as a final wash of the catalyst wet cake.3The weight percent of 4-[1-hydroxy-1-(2,3-dimethoxyphenyl)methyl]piperidine (11) and yield are based upon HPLC assay.
Workup
- customThe catalyst was removed by filtration
- washthe reactor and the catalyst were rinsed with 150 kg of methanol
- wash2 The reactor rinse filtrate
Sources & evidence
- ORD record
- ord-e3ebb7a8de8b4f759c98d53479fceff7
- Source dataset
- uspto-grants-2008_02
- Patent number
- US07332607B2
Reaction notes
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