Ethanol → 1-Tert-butoxycarbonyl-4-[4-(4-cyclohexylphenyl)piperazin-1-yl]piperidine

HRID 1977296Notes

Reaction equation

HRID 1977296 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:15]1([C:21]2[CH:26]=[CH:25][C:24]([N:27]3[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]3)=[CH:23][CH:22]=2)[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1.C(O)C.C([BH3-])#N.[Na+]>ClCCl.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:30]2[CH2:31][CH2:32][N:27]([C:24]3[CH:25]=[CH:26][C:21]([CH:15]4[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]4)=[CH:22][CH:23]=3)[CH2:28][CH2:29]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 702EthanolHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 27579961-(4-Cyclohexylphenyl)piperazineHCID 5003444Sodium cyanoborohydride

Product 1

HCID 219975301-Tert-butoxycarbonyl-4-[4-(4-cyclohexylphenyl)piperazin-1-yl]piperidineYield 19.3%

Reagents, catalysts & solvents 3

HCID 11026Titanium isopropoxideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of N-tert-butoxycarbonyl-4-piperidinone (3.3 g) and 1-(4-cyclohexylphenyl)piperazine (4.0 g) in dichloromethane (20 ml) was added titanium(IV)isopropoxide (8 ml) and the mixture was stirred at ambient temperature for 2 hours. Then, to the reaction mixture was added ethanol (20 ml) and sodium cyanoborohydride (1 g) in several portions, the reaction mixture was stirred at ambient temperature for 2 hours. The reaction mixture was pulverized with water. The precipitate was filtered off and the filtrate was extracted with dichloromethane. The organic layer was taken and dried over magnesium sulfate. Magnesium sulfate was filtered off, and the filtrate was evaporated under reduced pressure and chromatographed (Silica gel 60 (Trademark: prepared by Merck)) eluting with hexane/ethyl acetate to afford 1-tert-butoxycarbonyl-4-[4-(4-cyclohexylphenyl)piperazin-1-yl]piperidine (1.35 g).

Workup

  1. stirringthe reaction mixture was stirred at ambient temperature for 2 hours
  2. filtrationThe precipitate was filtered off
  3. extractionthe filtrate was extracted with dichloromethane
  4. dry with materialdried over magnesium sulfate
  5. filtrationMagnesium sulfate was filtered off
  6. customthe filtrate was evaporated under reduced pressure
  7. customchromatographed (Silica gel 60 (Trademark: prepared by Merck))
  8. washeluting with hexane/ethyl acetate

Sources & evidence

ORD record
ord-db293444a44a426cb3fdb3285072166b
Source dataset
uspto-grants-2001_05
Patent number
US06232290B1

Reaction notes

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