Ethanol → (+/-)-cis-1-[3,5-Bis(trifluoromethyl)benzoyl]-2-(phenylmethyl)-4-[4-(phenylmethyl)-1-piperazinyl]piperidine

HRID 1060189Notes

Reaction equation

HRID 1060189 reaction equation
[F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([CH:22]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:24]=1)[C:6]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH:9]1[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:7].[C:31]1([CH2:37][N:38]2[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]2)[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.C([BH3-])#N.[Na+].C(O)C>C(Cl)Cl.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].O>[F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([CH:22]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:24]=1)[C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([N:41]2[CH2:42][CH2:43][N:38]([CH2:37][C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=3)[CH2:39][CH2:40]2)[CH2:10][C@@H:9]1[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:7]

Participants

8

Reactant 4

HCID 702EthanolHCID 759941-BenzylpiperazineHCID 5003444Sodium cyanoborohydrideHCID 11026356(+/-)-1-[3,5-Bis(trifluoromethyl)benzoyl]-2-(phenylmethyl)-4-piperidinone

Product 1

HCID 86619157(+/-)-cis-1-[3,5-Bis(trifluoromethyl)benzoyl]-2-(phenylmethyl)-4-[4-(phenylmethyl)-1-piperazinyl]piperidineYield 26.9%

Reagents, catalysts & solvents 3

HCID 11026Titanium isopropoxideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

Titanium(IV)isopropoxide (16.5 g) was added to a mixture of intermediate 3 (21.5 g) and 1-(phenylmethyl)piperazine (8.81 g) in DCM (35 ml). The mixture was stirred for 3 hours at RT. Sodium cyanoborohydride (2.85 g) and ethanol (70 ml) were added and the resulting reaction mixture was stirred overnight at RT. Water (5 ml) and DCM were added. The biphasic mixture was filtered over dicalite, and the filter residue was washed with DCM. The organic layer was separated, dried, filtered and the solvent was evaporated. The residue was crystallized from CH3CN and the precipitate was filtered off and dried, yielding 7.93 g (26.9%) of (±)-cis-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(phenylmethyl)-4-[4-(phenylmethyl)-1-piperazinyl]piperidine (compound 16; mp. 143.8° C.).

Workup

  1. customthe resulting reaction mixture
  2. stirringwas stirred overnight at RT
  3. filtrationThe biphasic mixture was filtered over dicalite
  4. washthe filter residue was washed with DCM
  5. customThe organic layer was separated
  6. customdried
  7. filtrationfiltered
  8. customthe solvent was evaporated
  9. customThe residue was crystallized from CH3CN
  10. filtrationthe precipitate was filtered off
  11. customdried

Sources & evidence

ORD record
ord-7b761f7b615643d689884417a6ed5220
Source dataset
uspto-grants-2003_02
Patent number
US06521621B1

Reaction notes

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