Water → tert-butyl {[1-(4-cyano-2,6-difluorophenyl)-4-phenylpiperidin-3-yl]methyl}[(1R)-1-(1-naphthyl)ethyl]carbamate

HRID 1691693Notes

Reaction equation

HRID 1691693 reaction equation
[C:1]([O:5][C:6](=[O:33])[N:7]([C@@H:21]([C:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:26]=[CH:25][CH:24]=1)[CH3:22])[CH2:8][CH:9]1[CH:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:13][CH2:12][NH:11][CH2:10]1)([CH3:4])([CH3:3])[CH3:2].[F:34][C:35]1[CH:36]=[C:37]([CH:40]=[C:41]([F:44])[C:42]=1F)[C:38]#[N:39].C(=O)([O-])[O-].[K+].[K+].O>CS(C)=O>[C:38]([C:37]1[CH:36]=[C:35]([F:34])[C:42]([N:11]2[CH2:12][CH2:13][CH:14]([C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH:9]([CH2:8][N:7]([C@@H:21]([C:23]3[C:32]4[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=4)[CH:26]=[CH:25][CH:24]=3)[CH3:22])[C:6](=[O:33])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH2:10]2)=[C:41]([F:44])[CH:40]=1)#[N:39]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 5938143,4,5-TrifluorobenzonitrileHCID 59178636tert-butyl[(1R)-1-(1-naphthyl)ethyl][(4-phenylpiperidin-3-yl)methyl]carbamate

Product 1

HCID 66905675tert-butyl {[1-(4-cyano-2,6-difluorophenyl)-4-phenylpiperidin-3-yl]methyl}[(1R)-1-(1-naphthyl)ethyl]carbamateYield 73%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of 200 mg of tert-butyl[(1R)-1-(1-naphthyl)ethyl][(4-phenylpiperidin-3-yl)methyl]carbamate, 212 mg of 3,4,5-trifluorobenzonitrile, and 187 mg of potassium carbonate in 4.0 mL of DMSO was heated at 110° C. for 2 hours. The reaction mixture was cooled to room temperature, and water was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated brine in this order, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain 191 mg of tert-butyl {[1-(4-cyano-2,6-difluorophenyl)-4-phenylpiperidin-3-yl]methyl}[(1R)-1-(1-naphthyl)ethyl]carbamate as a colorless foamy substance. ESI+: 582

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe organic layer was washed with water and saturated brine in this order
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationAfter filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (hexane-ethyl acetate)

Sources & evidence

ORD record
ord-aa8dc8ecc1264739aa4de8ba4bb9325f
Source dataset
uspto-grants-2012_04
Patent number
US08153658B2

Reaction notes

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