Potassium Iodide → 2-Acetylamino-3,3-bis(4-fluorophenyl)propanoic acid

HRID 32868

반응식

HRID 32868 반응식
[C:1]([NH:4][CH:5](C(OCC)=O)[C:6]([O:8]CC)=[O:7])(=[O:3])[CH3:2].[H-].[Na+].[F:18][C:19]1[CH:24]=[CH:23][C:22]([C:25](Cl)(Cl)[C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)=[CH:21][CH:20]=1.[I-].[K+]>CN1CCCC1=O.O.C1(C)C=CC=CC=1>[C:1]([NH:4][CH:5]([CH:25]([C:26]1[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=1)[C:22]1[CH:23]=[CH:24][C:19]([F:18])=[CH:20][CH:21]=1)[C:6]([OH:8])=[O:7])(=[O:3])[CH3:2]

참가 물질

8

반응물 4

HCID 4875Potassium IodideHCID 14041Acetamidomalonic acid diethyl esterHCID 24758Sodium hydrideHCID 12714043Bis(4-fluorophenyl)methylene chloride

생성물 1

HCID 119778292-Acetylamino-3,3-bis(4-fluorophenyl)propanoic acid수율 104.4%

시약·촉매·용매 3

HCID 962Water용매HCID 1140Toluene용매HCID 13387N-methyl-2-pyrrolidone용매

실험 절차

To a solution of diethyl acetamidomalonate (22.79 g, 105.4 mmol) in N-methyl-2-pyrrolidone (84 mL) was added 55% sodium hydride (4.58 g, 105.2 mmol), and the mixture was stirred at room temperature for 1 hr. Bis(4-fluorophenyl)methylene chloride (16.5 mL, 84.7 mmol) and potassium iodide (13.95 g, 84.0 mmol) were added, and the mixture was stirred at 50° C. for 5 hrs. After completion of the reaction, toluene (200 mL) and water (100 mL) were added to the reaction mixture, and the mixture was partitioned. The obtained organic layer was washed twice with water (100 mL) and concentrated. Ethanol (108 mL) and 2M aqueous sodium hydroxide solution (127 mL) were added to the concentrated solution, and the mixture was stirred at 90° C. for 2.5 hrs. The reaction mixture was allowed to cool to 25° C., toluene (200 mL) and water (50 mL) were added, and the mixture was partitioned. The aqueous layer was concentrated to a half volume, and isopropyl acetate (60 mL) and water (130 mL) were added. The mixture was adjusted to pH 1.1 with concentrated hydrochloric acid and partitioned. The organic layer was washed with water (200 mL), concentrated and dried under vacuum to give the title compound (28.24 g).

후처리

  1. stirringthe mixture was stirred at 50° C. for 5 hrs
  2. additionwere added to the reaction mixture
  3. customthe mixture was partitioned
  4. washThe obtained organic layer was washed twice with water (100 mL)
  5. concentrationconcentrated
  6. additionEthanol (108 mL) and 2M aqueous sodium hydroxide solution (127 mL) were added to the concentrated solution
  7. stirringthe mixture was stirred at 90° C. for 2.5 hrs
  8. temperatureto cool to 25° C.
  9. additiontoluene (200 mL) and water (50 mL) were added
  10. customthe mixture was partitioned
  11. concentrationThe aqueous layer was concentrated to a half volume, and isopropyl acetate (60 mL) and water (130 mL)
  12. additionwere added
  13. custompartitioned
  14. washThe organic layer was washed with water (200 mL)
  15. concentrationconcentrated
  16. customdried under vacuum

출처 및 근거

ORD 기록
ord-6327e9d4ebee4f9e8e5a095143209a8b
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07427688B2

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