Thiophene → (+/-)-1,1-Dimethylethyl 4-[4-(acetylamino)-4-phenyl-1-piperidinyl]-2-(phenylmethyl)-1-piperidinecarboxylate

HRID 1699466Notes

Reaction equation

HRID 1699466 reaction equation
O=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH:4]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:3]1.[C:22]1([C:28]2([NH:34][C:35](=[O:37])[CH3:36])[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.S1C=CC=C1>CC(O)C.[Pt].CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[C:35]([NH:34][C:28]1([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:29][CH2:30][N:31]([CH:2]2[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH:4]([CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH2:3]2)[CH2:32][CH2:33]1)(=[O:37])[CH3:36]

Participants

7

Reactant 3

HCID 8030ThiopheneHCID 15886675N-(4-Phenylpiperidin-4-yl)acetamideHCID 183199211-Boc-2-benzylpiperidin-4-one

Product 1

HCID 18319927(+/-)-1,1-Dimethylethyl 4-[4-(acetylamino)-4-phenyl-1-piperidinyl]-2-(phenylmethyl)-1-piperidinecarboxylateYield 81.4%

Reagents, catalysts & solvents 3

HCID 11026Titanium isopropoxideCatalystHCID 23939PlatinumCatalystHCID 3776IsopropanolSolvent

Procedure

A mixture of (±)-1,1-dimethylethyl 4-oxo-2-(phenylmethyl)-1-piperidine carboxylate (0.1 mol) and N-(4-phenyl-4-piperidinyl)acetamide (0.1 mol) in 2-propanol (500 ml) was hydrogenated at 50° C. with platinum (4 g) as a catalyst in the presence of titanium(IV)isopropoxide (28.5 g) and thiophene (4%; 1 ml). After uptake of hydrogen, the catalyst was filtered off and the filtrate was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH 97/3). The pure fractions were collected and the solvent was evaporated, yielding 40 g (74.1%) of (±)-1,1-dimethylethyl 4-[4-(acetylamino)-4-phenyl-1-piperidinyl]-2-(phenylmethyl)-1-piperidinecarboxylate (intermediate 19).

Workup

  1. filtrationAfter uptake of hydrogen, the catalyst was filtered off
  2. customthe filtrate was evaporated
  3. customThe residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH 97/3)
  4. customThe pure fractions were collected
  5. customthe solvent was evaporated

Sources & evidence

ORD record
ord-7c48eb962fe540b793deef9d5ad6d414
Source dataset
uspto-grants-2002_02
Patent number
US06346540B1

Reaction notes

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