1-Benzyl-3-methyl-4-piperidone → (+,-)-2-(3,4-Dichlorophenyl)-4-[3,5-dimethylbenzoyl]-1-[[[3-methyl-1-(phenylmethyl)-4-piperidinyl]amino]acetyl]piperazine

HRID 362543Notes

Reaction equation

HRID 362543 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH:10]([CH3:15])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.BrC[C:18]([N:20]1[CH2:25][CH2:24][N:23]([C:26](=[O:35])[C:27]2[CH:32]=[C:31]([CH3:33])[CH:30]=[C:29]([CH3:34])[CH:28]=2)[CH2:22][CH:21]1[C:36]1[CH:41]=[CH:40][C:39]([Cl:42])=[C:38]([Cl:43])[CH:37]=1)=[O:19].[BH3-][C:45]#[N:46].[Na+]>CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].C(O)C>[Cl:43][C:38]1[CH:37]=[C:36]([CH:21]2[CH2:22][N:23]([C:26](=[O:35])[C:27]3[CH:28]=[C:29]([CH3:34])[CH:30]=[C:31]([CH3:33])[CH:32]=3)[CH2:24][CH2:25][N:20]2[C:18](=[O:19])[CH2:45][NH:46][CH:11]2[CH2:12][CH2:13][N:8]([CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH2:9][CH:10]2[CH3:15])[CH:41]=[CH:40][C:39]=1[Cl:42]

Participants

6

Reactant 3

HCID 5609651-Benzyl-3-methyl-4-piperidoneHCID 5003444Sodium cyanoborohydrideHCID 10277726(+,-)-Bromoacetyl-2-(3,4-dichlorophenyl)-4-(3,5-dimethylbenzoyl)piperazine

Product 1

HCID 15887547(+,-)-2-(3,4-Dichlorophenyl)-4-[3,5-dimethylbenzoyl]-1-[[[3-methyl-1-(phenylmethyl)-4-piperidinyl]amino]acetyl]piperazine

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 702EthanolSolvent

Procedure

A mixture of the ketone 4 from step 3 (70 mg, 0.13 mmol) and the compound 3 (34 mg, 0.17 mmol) was stirred in titanium isopropoxide (45 mg, 0.16 mmol) for 1.5 h. To the mixture were added ethanol (1.0 mL) and NaCNBH3 (5.4 mg, 8.6 mmol) and the mixture was stirred overnight. The reaction mixture was filtered and washed with EtOAc. The filtrate was washed with H2O and brine, dried with MgSO4 and concentrated. The residue was chromatographed on silica gel eluting with 5% NH3 sat. MeOH in CH2Cl2 to give both diastereomers pure.

Workup

  1. filtrationThe reaction mixture was filtered
  2. washwashed with EtOAc
  3. washThe filtrate was washed with H2O and brine
  4. dry with materialdried with MgSO4
  5. concentrationconcentrated
  6. customThe residue was chromatographed on silica gel eluting with 5% NH3 sat. MeOH in CH2Cl2
  7. customto give both diastereomers pure

Sources & evidence

ORD record
ord-9506181d93b546d6af2743e21e15dc4f
Source dataset
uspto-grants-1999_02
Patent number
US05869488

Reaction notes

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