Thiophene → (+/-)-1-(3,5-Dimethylbenzoyl)-2-(phenylmethyl)-4-piperidinone

HRID 991364Notes

Reaction equation

HRID 991364 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:21]=[C:22]([CH3:24])[CH:23]=1)[C:5]([N:7]1[CH2:12][CH2:11][C:10](=[O:13])[CH2:9][CH:8]1[CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:6].C1(C(C2C=CC=CC=2)N2CCNCC2)C=CC=CC=1.[O-]CCCC.[O-]CCCC.[O-]CCCC.[Al+3].S1C=CC=C1.[H][H]>C1(C)C=CC=CC=1.[Pd]>[C:15]1([CH2:14][CH:8]2[CH2:9][C:10](=[O:13])[CH2:11][CH2:12][NH:7]2)[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1.[CH3:24][C:22]1[CH:21]=[C:4]([CH:3]=[C:2]([CH3:1])[CH:23]=1)[C:5]([N:7]1[CH2:12][CH2:11][C:10](=[O:13])[CH2:9][CH:8]1[CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:6]

Participants

9

Reactant 5

HCID 8030ThiopheneHCID 70048BenzhydrylpiperazineHCID 6451513Aluminum butylateHCID 18630826(+/-)-1-(3,5-Dimethylbenzoyl)-2-(phenylmethyl)-4-piperidinoneHCID 178418361HCID 178418361, compound

Product 2

HCID 18630826(+/-)-1-(3,5-Dimethylbenzoyl)-2-(phenylmethyl)-4-piperidinoneHCID 186308462-Benzylpiperidin-4-one

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 1140TolueneSolvent

Procedure

A mixture of intermediate 2 (3.2 g), 1-(diphenylmethyl) piperazine (2.5 g) and aluminum tributoxide (2 g) in toluene (250 ml) was hydrogenated for 48 hours at 50° C., with palladium on activated carbon (10%; 2 g) as a catalyst in the presence of thiophene (4% solution; 1 ml). After uptake of hydrogen (1 equiv), the catalyst was filtered off and the filtrate was evaporated. The residue was purified by high-performance liquid chromatography over silica gel (eluent: CH2Cl2/CH3OH 100/0, upgrading to 90/10). Two pure fractions were collected and their solvent was evaporated, resulting in residue 1 and residue 2. Residue 1 was suspended in DIPE. The precipitate was filtered off and dried, yielding 0.94 g (17%) of (±)-cis-1-(dimethylbenzoyl)-4-[4-(diphenylmethyl)-1-piperazinyl]-2-(phenylmethyl) piperidine (compound 12; mp. 100.8° C.). Residue 2 was dried, yielding 0.2 g (3.6%) of (±)-trans-1-(dimethylbenzoyl)-4-[4-(diphenylmethyl)-1-piperazinyl]-2-(phenylmethyl)piperidine (compound 13).

Workup

  1. customthe filtrate was evaporated
  2. customThe residue was purified by high-performance liquid chromatography over silica gel (eluent: CH2Cl2/CH3OH 100/0, upgrading to 90/10)
  3. customTwo pure fractions were collected
  4. customtheir solvent was evaporated

Sources & evidence

ORD record
ord-d86f4258c27a4e7babe09e3c8a108311
Source dataset
uspto-grants-2002_10
Patent number
USRE037886E1

Reaction notes

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