Ethyl chloroformate → HCID 68958899, compound

HRID 270041Notes

Reaction equation

HRID 270041 reaction equation
C([N:8]1[CH2:13][CH2:12][C:11]2([CH2:17][C:16]3[CH:18]=[C:19]([C:22]([F:25])([F:24])[F:23])[CH:20]=[CH:21][C:15]=3[O:14]2)[CH2:10][CH2:9]1)C1C=CC=CC=1.C(OC(Cl)=O)C>C1(C)C=CC=CC=1>[F:25][C:22]([F:23])([F:24])[C:19]1[CH:20]=[CH:21][C:15]2[O:14][C:11]3([CH2:10][CH2:9][NH:8][CH2:13][CH2:12]3)[CH2:17][C:16]=2[CH:18]=1

Participants

4

Reactant 2

HCID 10928Ethyl chloroformateHCID 68961699HCID 68961699, compound

Product 1

HCID 68958899HCID 68958899, compoundYield 75.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

To a solution of 1′-benzyl-5-(trifluoromethyl)-3H-spiro[1-benzofuran-2,4′-piperidin] (280 mg, 0.806 mmol) in toluene (3 mL) was added ethylchloroformate (0.093 mL, 0.967 mmol) and the reaction mixture was stirred at reflux temperature overnight, cooled to room temperature, diluted by addition of toluene and washed with aqueous NaHCO3 and water successively. The organic layer was dried over Na2SO4, filtered and concentrated. The residue was dissolved in ethanol ((4 mL), aqueous KOH (1.14 g KOH in 1.2 mL of H2O) was added and the reaction mixture was refluxed overnight, cooled to room temperature, ethanol was removed in vacuo. Aqueous layer was extracted with Et2O, combined ether layer was washed with 3N aqueous HCl. Combined acidic layer was made pH 10 by addition of aqueous NaOH. The basic solution was extracted with ethyl acetate. The combined organic layer was washed with water, dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel flash chromatography (0-2% methanol in dichloromethane, 0.2% NH4OH) to give the subtitled compound (156 mg).

Workup

  1. temperatureat reflux temperature overnight
  2. washwashed with aqueous NaHCO3 and water successively
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved in ethanol ((4 mL), aqueous KOH (1.14 g KOH in 1.2 mL of H2O)
  7. additionwas added
  8. temperaturethe reaction mixture was refluxed overnight
  9. temperaturecooled to room temperature
  10. customethanol was removed in vacuo
  11. extractionAqueous layer was extracted with Et2O, combined ether layer
  12. washwas washed with 3N aqueous HCl
  13. additionby addition of aqueous NaOH
  14. extractionThe basic solution was extracted with ethyl acetate
  15. washThe combined organic layer was washed with water
  16. dry with materialdried over Na2SO4
  17. filtrationfiltered
  18. concentrationconcentrated
  19. customThe residue was purified by silica gel flash chromatography (0-2% methanol in dichloromethane, 0.2% NH4OH)

Sources & evidence

ORD record
ord-2dbc174c53524bd1a38d47baef22e288
Source dataset
uspto-grants-2008_11
Patent number
US07449475B2

Reaction notes

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