1-Phenethylamine → (+)-Ethyl cis-3-methoxy-4-[(1-phenylethyl)amino]-1-piperidinecarboxylate

HRID 345576Notes

Reaction equation

HRID 345576 reaction equation
Cl.ClCC1C=CC(N2C=CN=C2)=CC=1.[CH3:15][O:16][CH:17]1[C:22](=O)[CH2:21][CH2:20][N:19]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:18]1.[CH3:29][CH:30]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[NH2:31].S1C=CC=C1.[H][H]>C(O)C.[Pd].CO>[CH3:15][O:16][C@H:17]1[C@@H:22]([NH:31][CH:30]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH3:29])[CH2:21][CH2:20][N:19]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:18]1

Participants

9

Reactant 5

HCID 74081-PhenethylamineHCID 8030ThiopheneHCID 2724451Ethyl 3-methoxy-4-oxopiperidine-1-carboxylateHCID 197946621-[4-(chloromethyl)phenyl]-1H-imidazole hydrochlorideHCID 178418361HCID 178418361, compound

Product 1

HCID 67914576(+)-Ethyl cis-3-methoxy-4-[(1-phenylethyl)amino]-1-piperidinecarboxylateYield 51%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 887MethanolSolvent

Procedure

A solution of 20 parts of ethyl 3-methoxy-4-oxo-1-piperidinecarboxylate, 12 parts of (-)-α-methylbenzenemethanamine, 2 parts of a solution of thiophene in ethanol 4% and 200 parts of methanol was hydrogenated at normal pressure and at room temperature with 4 parts of palladium-on-charcoal catalyst 10%. After the calculated amount of hydrogen was taken up, the catalyst was filtered off and the filtrate was evaporated in vacuo. The residue was purified by HPLC using a mixture of hexane, trichloromethane and methanol (50:49.5:0.5 by volume) as eluent. The pure A-fractions were collected and the eluent was evaporated, yielding 15.62 parts (51%) of (-)-ethyl cis-3-methoxy-4-[(1-phenylethyl)amino]-1-piperidinecarboxylate as a residue (intermediate 103).

Workup

  1. filtrationthe catalyst was filtered off
  2. customthe filtrate was evaporated in vacuo
  3. customThe residue was purified by HPLC
  4. additiona mixture of hexane, trichloromethane and methanol (50:49.5:0.5 by volume) as eluent
  5. customThe pure A-fractions were collected
  6. customthe eluent was evaporated

Sources & evidence

ORD record
ord-57194a63cb7d4511a02e1f1861792cf9
Source dataset
uspto-grants-1991_10
Patent number
US05057525

Reaction notes

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