Dimethylformamide → 4-(3-{1-[3-(4-Cyanophenoxy)propyl]-4-piperidinyl}propoxy)-2-fluorobenzonitrile

HRID 881030Notes

Reaction equation

HRID 881030 reaction equation
CN(C)C=O.[F:6][C:7]1[CH:14]=[C:13]([O:15][CH2:16][CH2:17][CH2:18][CH:19]2[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)[CH:12]=[CH:11][C:8]=1[C:9]#[N:10].C(=O)([O-])[O-].[K+].[K+].Br[CH2:32][CH2:33][CH2:34][O:35][C:36]1[CH:43]=[CH:42][C:39]([C:40]#[N:41])=[CH:38][CH:37]=1>C1(C)C=CC=CC=1.O.C(OCC)(=O)C>[C:40]([C:39]1[CH:42]=[CH:43][C:36]([O:35][CH2:34][CH2:33][CH2:32][N:22]2[CH2:23][CH2:24][CH:19]([CH2:18][CH2:17][CH2:16][O:15][C:13]3[CH:12]=[CH:11][C:8]([C:9]#[N:10])=[C:7]([F:6])[CH:14]=3)[CH2:20][CH2:21]2)=[CH:37][CH:38]=1)#[N:41]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 10879224HCID 10879224, compoundHCID 59263044HCID 59263044, compound

Product 1

HCID 686904254-(3-{1-[3-(4-Cyanophenoxy)propyl]-4-piperidinyl}propoxy)-2-fluorobenzonitrileYield 42.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To an N,N-dimethylformamide solution (2.0 mL) of 0.10 g of 2-fluoro-4-[3-(4-piperidinyl)propoxy]benzonitrile were sequentially added 0.10 g of potassium carbonate and 0.13 g of 4-(3-bromopropoxy)benzonitrile at room temperature, which was then stirred at the same temperature for 13 hours. Ethyl acetate, water, and toluene were added to the reaction mixture. The organic layer was separated and dried with anhydrous sodium sulfate, followed by distilling off the solvent under reduced pressure. The resultant residue was purified using silica gel column chromatography (eluent; chloroform:methanol=4:1) to provide 68 mg of 4-(3-{1-[3-(4-cyanophenoxy)propyl]-4-piperidinyl}propoxy)-2-fluorobenzonitrile as white solid form.

Workup

  1. customat room temperature
  2. customThe organic layer was separated
  3. dry with materialdried with anhydrous sodium sulfate
  4. distillationby distilling off the solvent under reduced pressure
  5. customThe resultant residue was purified

Sources & evidence

ORD record
ord-be6d558e099b49f199c57635154d98fc
Source dataset
uspto-grants-2015_03
Patent number
US08993603B2

Reaction notes

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