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

HRID 2112731ノート

反応式

HRID 2112731 の反応式
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

参加物

4

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒2 回

実験手順

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 mixture was refluxed over night, cooled to room temperature, diluted by addition of toluene (10 mL), washed successively with saturated aqueous NaHCO3 solution and water. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. The residue was dissolved in ethanol (3.5 mL), aqueous KOH (800 mg, KOH in 0.8 mL H2O) was added and the mixture was refluxed over night, cooled to room temperature, ethanol was removed in vacuo. Aqueous layer was extracted with diethyl ether. Combined ether layer is was washed with 3N aqueous HCl. Aqueous layer was adjusted to pH 10 by addition of aqueous 3N NaOH. The basic solution was extracted with ethyl acetate. Combined organic layer was washed with water, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by HPLC (10-55% CH3CN in H2O, 0.1% NH4OH) to give the title compound (49 mg). 1H-NMR (CD3OD, 400 MHz): δ 6.92-6.87 (m, 1H); 6.81-6.75 (m, 1H); 6.64 (dd, J=4.2, 8.7 Hz, 1H); 3.08-2.98 (m, 4H); 2.89-2.81 (m, 2H); 1.91-1.83 (m, 2H); 1.78-1.69 (m, 2H).

後処理

  1. temperaturethe mixture was refluxed over night
  2. washwashed successively with saturated aqueous NaHCO3 solution and water
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was dissolved in ethanol (3.5 mL)
  7. additionaqueous KOH (800 mg, KOH in 0.8 mL H2O) was added
  8. temperaturethe mixture was refluxed over night
  9. temperaturecooled to room temperature
  10. customethanol was removed in vacuo
  11. extractionAqueous layer was extracted with diethyl ether
  12. washCombined ether layer is was washed with 3N aqueous HCl
  13. additionAqueous layer was adjusted to pH 10 by addition of aqueous 3N NaOH
  14. extractionThe basic solution was extracted with ethyl acetate
  15. washCombined organic layer was washed with water
  16. dry with materialdried over Na2SO4
  17. filtrationfiltered
  18. concentrationconcentrated in vacuo
  19. customThe residue was purified by HPLC (10-55% CH3CN in H2O, 0.1% NH4OH)

出典と根拠

ORDレコード
ord-1b5bbe29eee843cf958968978943d19d
出典データセット
uspto-grants-2009_04
特許番号
US07524856B2

反応ノート

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