Potassium Carbonate → Tert-butyl 4-[3-fluoro(4-fluorobenzyl)anilino]-1-piperidinecarboxylate

HRID 1724666Notes

Reaction equation

HRID 1724666 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][CH:21]=1)[NH:5][CH:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:29][C:30]1[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=1>C(#N)C>[F:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][CH:21]=1)[N:5]([CH2:29][C:30]1[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=1)[CH:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:16])[CH3:17])=[O:13])[CH2:8][CH2:7]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 680214-Fluorobenzyl bromideHCID 23137591tert-Butyl 4-(3-fluoroanilino)piperidine-1-carboxylate

Product 1

HCID 9978463Tert-butyl 4-[3-fluoro(4-fluorobenzyl)anilino]-1-piperidinecarboxylateYield 89%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Tert-butyl 4-(3-fluoroanilino)-1-piperidinecarboxylate 1 (20 g) was dissolved in acetonitrile (250 ml). Potassium carbonate (33.2 g) and 1-(bromomethyl)-4-fluorobenzene (11 ml) were added to the solution. The reaction mixture was heated at reflux overnight, then cooled, concentrated and the residue was taken up in dichloromethane and water. The aqueous layer was washed twice with dichloromethane. The combined organic layers were dried over MgSO4 and concentrated. The resulting white solid was triturated in hexane and filtered off to afford tert-butyl 4-[3-fluoro(4-fluorobenzyl)anilino]-1-piperidinecarboxylate 8 (25.5 g).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux overnight
  3. temperaturecooled
  4. concentrationconcentrated
  5. washThe aqueous layer was washed twice with dichloromethane
  6. dry with materialThe combined organic layers were dried over MgSO4
  7. concentrationconcentrated
  8. customThe resulting white solid was triturated in hexane
  9. filtrationfiltered off

Sources & evidence

ORD record
ord-7c978580178a4efaaef486768faac47a
Source dataset
uspto-grants-2009_02
Patent number
US07488741B2

Reaction notes

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