Dimethyl Sulfoxide → methyl 4-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-phenylpiperidin-1-yl]-3,5-difluorobenzoate

HRID 1691764Notes

Reaction equation

HRID 1691764 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([F:13])[C:11]=1F)[C:5]([O:7][CH3:8])=[O:6].C(=O)([O-])[O-].[K+].[K+].CS(C)=O.[C:24]1([C@H:34]([N:36]([CH2:44][CH:45]2[CH2:50][CH2:49][NH:48][CH2:47][CH:46]2[C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)[C:37](=[O:43])[O:38][C:39]([CH3:42])([CH3:41])[CH3:40])[CH3:35])[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH:27]=[CH:26][CH:25]=1>C1COCC1.O>[C:39]([O:38][C:37]([N:36]([CH2:44][CH:45]1[CH2:50][CH2:49][N:48]([C:11]2[C:10]([F:13])=[CH:9][C:4]([C:5]([O:7][CH3:8])=[O:6])=[CH:3][C:2]=2[F:1])[CH2:47][CH:46]1[C:51]1[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=1)[C@@H:34]([C:24]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH:27]=[CH:26][CH:25]=1)[CH3:35])=[O:43])([CH3:40])([CH3:41])[CH3:42]

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 11430Potassium CarbonateHCID 2783211Methyl 3,4,5-trifluorobenzoateHCID 59178521HCID 59178521, compound

Product 1

HCID 66906144methyl 4-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-phenylpiperidin-1-yl]-3,5-difluorobenzoate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of 116 mg of methyl 3,4,5-trifluorobenzoate, 113 mg of potassium carbonate, and 2.0 mL of DMSO was added 181 mg of a solution of tert-butyl [(1R)-1-(1-naphthyl)ethyl][(3-phenylpiperidin-4-yl)methyl]carbamate in 3.0 mL of THF at room temperature. It was stirred at 100° C. overnight, and then cooled. To the reaction mixture was added water, followed by extraction with ethyl acetate, and the organic layer was then washed with water and saturated brine in this order, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure to obtain 248 mg of methyl 4-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-phenylpiperidin-1-yl]-3,5-difluorobenzoate as a crude product. FAB+: 615

Workup

  1. temperaturecooled
  2. extractionfollowed by extraction with ethyl acetate
  3. washthe organic layer was then washed with water and saturated brine in this order
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationAfter filtration
  6. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-8a3d8ab748ce43f29d56440161c5f8a0
Source dataset
uspto-grants-2012_04
Patent number
US08153658B2

Reaction notes

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