Potassium Carbonate → Ethyl 4-oxobutanoate

HRID 221835노트

반응식

HRID 221835 반응식
[CH2:1]([O:3][C:4](=[O:22])[CH2:5][CH2:6][C:7](C1C=C(F)C(OCCCCl)=C(F)C=1)=[O:8])[CH3:2].C([O-])([O-])=O.[K+].[K+].C1(S([O-])(=O)=O)C=CC=CC=1>CC#N.[Na+].[I-]>[CH2:1]([O:3][C:4](=[O:22])[CH2:5][CH2:6][CH:7]=[O:8])[CH3:2]

참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 91526BenzenesulfonateHCID 596518884-[4-(3-Chloropropoxy)-3,5-difluorophenyl]-4-oxo-butyric acid ethyl ester

생성물 1

HCID 82395Ethyl 4-oxobutanoate수율 204.7%

시약·촉매·용매 2

HCID 5238Sodium Iodide촉매HCID 6342Acetonitrile용매

실험 절차

A mixture of 4-[4-(3-chloropropoxy)-3,5-difluorophenyl]-4-oxo-butyric acid ethyl ester (5 g, 14.9 mmol), K2CO3 (7.2 g, 52.1 mmol), NaI (220 mg, 1.4 mmol), and Benzenesulfonate; (R)-methylpyrrolidinium (8 g, 33 mmol) in CH3CN (110 mL) was heated under argon at 80° C. for 36 h. The reaction was concentrated and partitioned between saturated aqueous sodium bicarbonate solution and methylene chloride. The aqueous layer was extracted twice with methylene chloride and the combined organics was washed with brine, dried (Na2SO4), filtered, and concentrated to provide a crude material (96% purity). The crude material was purified by ISCO (80 g silica gel column) chromatography using 2% to 9% methanol in methylene chloride to 10% methanol containing 0.1% ammonium hydroxide in methylene chloride. The isolated material was dissolved in methylene chloride and washed with saturated aqueous sodium bicarbonate solution, brine, dried (Na2SO4), filtered, and concentrated. The isolated material was crystallized with a mixture of methylene chloride, ether and hexane to obtain 4-{3,5-difluoro-4-[3-(R)-2-methyl-pyrrolidin-1-yl)-propoxy]-phenyl}-4-oxo-butyric acid ethyl ester (3.97 g, 70%, 99% purity), MS m/z=384 (M+H).

후처리

  1. concentrationThe reaction was concentrated
  2. custompartitioned between saturated aqueous sodium bicarbonate solution and methylene chloride
  3. extractionThe aqueous layer was extracted twice with methylene chloride
  4. washthe combined organics was washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto provide a crude material (96% purity)
  9. customThe crude material was purified by ISCO (80 g silica gel column) chromatography
  10. dissolutionThe isolated material was dissolved in methylene chloride
  11. washwashed with saturated aqueous sodium bicarbonate solution, brine
  12. dry with materialdried (Na2SO4)
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customThe isolated material was crystallized with a mixture of methylene chloride, ether and hexane

출처 및 근거

ORD 기록
ord-51691f3b3d324b0ca16459278fb1898c
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08207168B2

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