Methyl Ethyl Ketone → Tert-butyl 4-[3-(4-cyano-3-fluorophenoxy)propyl]-1-piperidinecarboxylate

HRID 881028Notes

Reaction equation

HRID 881028 reaction equation
CC(=O)CC.Br[CH2:7][CH2:8][CH2:9][CH:10]1[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]1.[F:23][C:24]1[CH:31]=[C:30]([OH:32])[CH:29]=[CH:28][C:25]=1[C:26]#[N:27].C(=O)([O-])[O-].[K+].[K+]>O.C(OCC)(=O)C>[C:26]([C:25]1[CH:28]=[CH:29][C:30]([O:32][CH2:7][CH2:8][CH2:9][CH:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]2)=[CH:31][C:24]=1[F:23])#[N:27]

Participants

7

Reactant 4

HCID 6569Methyl Ethyl Ketone2×HCID 11430Potassium CarbonateHCID 27346752-Fluoro-4-hydroxybenzonitrileHCID 18409081tert-Butyl 4-(3-bromopropyl)piperidine-1-carboxylate

Product 1

HCID 59263029Tert-butyl 4-[3-(4-cyano-3-fluorophenoxy)propyl]-1-piperidinecarboxylateYield 54.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

A 2-butanone (7.6 mL) solution of 1.12 g of tert-butyl 4-(3-bromopropyl)-1-piperidinecarboxylate was added to a 2-butanone (7.0 mL) mixture of 0.50 g of 2-fluoro-4-hydroxybenzonitrile and 0.56 g of potassium carbonate, which was then heated to reflux for 6 hours and 30 minutes. After cooling down to room temperature, the reaction mixture was added to a mixture of ethyl acetate and water. The organic layer was separated, washed with water, and dried with anhydrous magnesium sulfate, followed by distilling off the solvent under reduced pressure. The resultant residue was purified using silica gel column chromatography (eluent; hexane:ethyl acetate=4:1) to provide 0.72 g of tert-butyl 4-[3-(4-cyano-3-fluorophenoxy)propyl]-1-piperidinecarboxylate as colorless oily form.

Workup

  1. temperaturewas then heated
  2. temperatureto reflux for 6 hours and 30 minutes
  3. customThe organic layer was separated
  4. washwashed with water
  5. dry with materialdried with anhydrous magnesium sulfate
  6. distillationby distilling off the solvent under reduced pressure
  7. customThe resultant residue was purified

Sources & evidence

ORD record
ord-eafa19f91cf043eda6de1d2bfb89bf42
Source dataset
uspto-grants-2015_03
Patent number
US08993603B2

Reaction notes

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