Water → tert-butyl (3R,4R)-4-{[(4-bromophenyl)carbonyl](methyl)amino}-3-(3,4-dichlorophenyl)piperidine-1-carboxylate

HRID 1260985Notes

Reaction equation

HRID 1260985 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([NH:10][C@@H:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][C@H:12]2[C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[C:26]([Cl:31])[CH:25]=2)=[O:9])=[CH:4][CH:3]=1.[H-].[Na+].[CH3:34]I.O>CN(C=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([N:10]([CH3:34])[C@@H:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][C@H:12]2[C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[C:26]([Cl:31])[CH:25]=2)=[O:9])=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 86631418tert-butyl (3R,4R)-4-{[(4-bromophenyl)carbonyl]amino}-3-(3,4-dichlorophenyl)piperidine-1-carboxylate

Product 1

HCID 86631417tert-butyl (3R,4R)-4-{[(4-bromophenyl)carbonyl](methyl)amino}-3-(3,4-dichlorophenyl)piperidine-1-carboxylateYield 92%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of the compound (1.16 g) obtained in step 1 in DMF (22 mL) was added sodium hydride (60% in oil, 175 mg) at 0° C., and the mixture was stirred for 10 min. Then, methyl iodide (681 μL) was added, and the mixture was stirred overnight at room temperature. To the reaction mixture was added water, and the resultant product was extracted with ethyl acetate. The organic layer was washed with brine and dried, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (solvent gradient; 10→90% ethyl acetate/hexane) to give tert-butyl (3R,4R)-4-{[(4-bromophenyl)carbonyl](methyl)amino}-3-(3,4-dichlorophenyl)piperidine-1-carboxylate (1.09 g, 92%) as a white powder.

Workup

  1. stirringthe mixture was stirred overnight at room temperature
  2. extractionthe resultant product was extracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. customdried
  5. customthe solvent was evaporated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (solvent gradient; 10→90% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-247558f532de4546838dea5ae471ca1a
Source dataset
uspto-grants-2013_06
Patent number
US08470816B2

Reaction notes

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