p-Toluenesulfonic acid → 2-(4-Fluoro-2-methylphenyl)piperidin-4-one

HRID 1178312노트

반응식

HRID 1178312 반응식
[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[C:4]([CH3:10])[CH:3]=1.C1O[C:14]([CH2:16][CH2:17][NH2:18])([CH3:15])[O:13]C1.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)([O-])[O-].[K+].[K+]>C1C=CC=CC=1.CCOC(C)=O>[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]2[CH2:15][C:14](=[O:13])[CH2:16][CH2:17][NH:18]2)=[C:4]([CH3:10])[CH:3]=1

참가 물질

7

반응물 4

HCID 6101p-Toluenesulfonic acidHCID 11430Potassium CarbonateHCID 27832174-Fluoro-2-methylbenzaldehydeHCID 109424562-(2-Methyl-1,3-dioxolan-2-yl)ethanamine

생성물 1

HCID 219276772-(4-Fluoro-2-methylphenyl)piperidin-4-one수율 41.7%

시약·촉매·용매 2

HCID 241Benzene용매2회HCID 8857Ethyl Acetate용매

실험 절차

4-Fluoro-2-methyl-benzaldehyde (4 g) was added to a solution of 4-aminobutan-2-one ethylene acetal (3.8 g) in dry benzene (50 mL) and the solution was stirred at r.t. under a nitrogen atmosphere. After 1 hour the mixture was heated at reflux for 16 hours and then allowed to cool to r.t. This solution was slowly added to a refluxing solution of p-toluensulphonic acid (10.6 g) in dry benzene (50 mL) previously refluxed for 1 hour with a Dean-Stark apparatus. After 3.5 hours the crude solution was cooled and made basic with a saturated potassium carbonate solution and taken up with AcOEt (50 mL). The aqueous phase was extracted with AcOEt (3×50 mL) and Et2O (2×50 mL). The organic layer was dried and concentrated in vacuo to a yellow thick oil as residue (7.23 g). A portion of the crude mixture (3 g) was dissolved in a 6N hydrochloric acid solution (20 mL) and stirred at 60° C. for 16 hours. The solution was basified with solid potassium carbonate and extracted with DCM (5×50 mL). The combined organic phases were washed with brine (50 mL), dried and concentrated in vacuo to give the title compound (2.5 g) as a thick yellow oil.

후처리

  1. temperatureAfter 1 hour the mixture was heated
  2. temperatureat reflux for 16 hours
  3. temperatureto cool to r.t
  4. temperaturepreviously refluxed for 1 hour with a Dean-Stark apparatus
  5. extractionThe aqueous phase was extracted with AcOEt (3×50 mL) and Et2O (2×50 mL)
  6. customThe organic layer was dried
  7. concentrationconcentrated in vacuo to a yellow thick oil as residue (7.23 g)
  8. dissolutionA portion of the crude mixture (3 g) was dissolved in a 6N hydrochloric acid solution (20 mL)
  9. stirringstirred at 60° C. for 16 hours
  10. extractionextracted with DCM (5×50 mL)
  11. washThe combined organic phases were washed with brine (50 mL)
  12. customdried
  13. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-01649125b5d2445e961da2916c468aed
출처 데이터셋
uspto-grants-2007_10
특허 번호
US07276509B2

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