Ethyl chloroformate → 5-Fluoro-3H-spiro[benzofuran-2,4'-piperidine]

HRID 270096Notes

Reaction equation

HRID 270096 reaction equation
ClC(OCC)=O.C([N:14]1[CH2:19][CH2:18][C:17]2([CH2:23][C:22]3[CH:24]=[C:25]([F:28])[CH:26]=[CH:27][C:21]=3[O:20]2)[CH2:16][CH2:15]1)C1C=CC=CC=1>C1(C)C=CC=CC=1>[F:28][C:25]1[CH:26]=[CH:27][C:21]2[O:20][C:17]3([CH2:16][CH2:15][NH:14][CH2:19][CH2:18]3)[CH2:23][C:22]=2[CH:24]=1

Participants

4

Reactant 2

HCID 10928Ethyl chloroformateHCID 598336291'-Benzyl-5-fluoro-3H-spiro[1-benzofuran-2,4'-piperidine]

Product 1

HCID 574943045-Fluoro-3H-spiro[benzofuran-2,4'-piperidine]Yield 46.9%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

Ethyl chloroformate (65.6 mg, 0.604 mmol) was added to a solution of 1′-benzyl-5-fluoro-3H-spiro[1-benzofuran-2,4′-piperidine] (150 mg, 0.504 mmol) in toluene (2 mL) and the reaction mixture was refluxed overnight. The reaction mixture was cooled to room temperature, diluted by addition of toluene, washed successively with aqueous sodium hydrogencarbonate (NaHCO3) and water. The organic layer was dried over sodium sulphate (Na2SO4) filtered and concentrated in vacuo. The residue was dissolved in ethanol (3.5 mL), aqueous potassium hydroxide (KOH) (800 mg KOH in 0.8 mL water) was added and the reaction mixture was kept on stirring at reflux overnight, cooled to room temperature, extracted with ethyl acetate. The organic layer was well washed with water, dried over sodium sulphate (Na2SO4), filtered and concentrated. The residue was purified by HPLC (10% acetonitrile (CH3CN)-55% CH3CN in water containing 0.1% ammonium hydroxide, NH4OH) to give the titled compound (49 mg).

Workup

  1. temperaturethe reaction mixture was refluxed overnight
  2. washwashed successively with aqueous sodium hydrogencarbonate (NaHCO3) and water
  3. dry with materialThe organic layer was dried over sodium sulphate (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was dissolved in ethanol (3.5 mL)
  7. additionaqueous potassium hydroxide (KOH) (800 mg KOH in 0.8 mL water) was added
  8. temperatureat reflux overnight
  9. temperaturecooled to room temperature
  10. extractionextracted with ethyl acetate
  11. washThe organic layer was well washed with water
  12. dry with materialdried over sodium sulphate (Na2SO4)
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customThe residue was purified by HPLC (10% acetonitrile (CH3CN)-55% CH3CN in water containing 0.1% ammonium hydroxide, NH4OH)

Sources & evidence

ORD record
ord-116f5196812e4ba8b668c7ac2b29e238
Source dataset
uspto-grants-2008_11
Patent number
US07449475B2

Reaction notes

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