tert-Butyl 4-oxopiperidine-1-carboxylate → HCID 68743595, compound

HRID 2244898Notes

Reaction equation

HRID 2244898 reaction equation
Cl.Cl.[CH3:3][C@H:4]1[CH2:9][NH:8][CH2:7][CH2:6][N:5]1[CH:10]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([C:19]([F:22])([F:21])[F:20])[CH:17]=2)[CH2:12][CH2:11]1.O=[C:24]1[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]1.[C-:37]#[N:38].C([Al+]CC)C>ClCCl.CC(C)[O-].CC(C)[O-].CC(C)[O-].CC(C)[O-].[Ti+4]>[C:37]([C:24]1([N:8]2[CH2:7][CH2:6][N:5]([CH:10]3[C:18]4[C:13](=[CH:14][CH:15]=[C:16]([C:19]([F:22])([F:20])[F:21])[CH:17]=4)[CH2:12][CH2:11]3)[C@@H:4]([CH3:3])[CH2:9]2)[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]1)#[N:38]

Participants

6

Reactant 3

HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 16686413Diethyl aluminum cyanideHCID 68742203HCID 68742203, compound

Product 1

HCID 68743595HCID 68743595, compoundYield 112.4%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 6344DichloromethaneSolvent

Procedure

(2S)-2-Methyl-1-[6-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]piperazine dihydrochloride (0.38 g, 1.3 mmol) was dissolved in dichloromethane. The solution was washed with saturated NaHCO3 solution, dried over MgSO4 and concentrated. The residue was taken up in dichloromethane (20 mL). To it were added tert-butyl 4-oxo-1-piperidinecarboxylate (0.32 g, 1.6 mmol) and titanium tetraisopropoxide (0.8 g, 3 mmol). The mixture was stirred at room temperature overnight and concentrated in vacuo. The residue was taken up in THF (20 mL). Diethylaluminum cyanide (0.18 g, 1.6 mmol) was added. After being stirred at room temperature for 5 hrs, the solution was quenched by addition of water (3 mL). The resulting solution was filtered through Celite and the Celite was washed with dichloromethane several times. The filtrate was dried over MgSO4 and concentrated to give the title compound (0.72 g, 98%) as a brown viscous oil. MS calculated for C26H35F3N4O2: (M+H)+ 493; found 493.2.

Workup

  1. washThe solution was washed with saturated NaHCO3 solution
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated
  4. concentrationconcentrated in vacuo
  5. stirringAfter being stirred at room temperature for 5 hrs
  6. customthe solution was quenched by addition of water (3 mL)
  7. filtrationThe resulting solution was filtered through Celite
  8. washthe Celite was washed with dichloromethane several times
  9. dry with materialThe filtrate was dried over MgSO4
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-7c777e0d103b4cdd8963b23e6ae6011a
Source dataset
uspto-grants-2010_03
Patent number
US07678798B2

Reaction notes

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