Citric Acid → 1,3-Diethyl 2-[2-(4-bromo-2-chlorophenyl)ethyl]-2-[[(1,1-dimethylethoxy)carbonyl]amino]propanedioate

HRID 1641536노트

반응식

HRID 1641536 반응식
[CH2:1]([O:3][C:4](=[O:19])[CH:5]([NH:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH3:2].CC(C)([O-])C.[Na+].[Br:26][C:27]1[CH:32]=[CH:31][C:30]([CH2:33][CH2:34]I)=[C:29]([Cl:36])[CH:28]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1.CN(C)C=O>[Br:26][C:27]1[CH:32]=[CH:31][C:30]([CH2:33][CH2:34][C:5]([NH:11][C:12]([O:14][C:15]([CH3:17])([CH3:16])[CH3:18])=[O:13])([C:4]([O:3][CH2:1][CH3:2])=[O:19])[C:6]([O:8][CH2:9][CH3:10])=[O:7])=[C:29]([Cl:36])[CH:28]=1

참가 물질

7

반응물 4

HCID 311Citric AcidHCID 382219Diethyl 2-((tert-butoxycarbonyl)amino)malonateHCID 23676156Sodium t-butoxideHCID 462025614-Bromo-2-chloro-1-(2-iodoethyl)benzene

생성물 1

HCID 462028801,3-Diethyl 2-[2-(4-bromo-2-chlorophenyl)ethyl]-2-[[(1,1-dimethylethoxy)carbonyl]amino]propanedioate수율 64.7%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8028Tetrahydrofuran용매2회

실험 절차

Diethyl(tert-butoxycarbonyl)aminomalonate (202 g) was dissolved in a mixed solution of tetrahydrofuran (6000 mL) and N,N-dimethylformamide (714 mL), and sodium tert-butoxide (70.5 g) was added. After heating the mixture to the refluxing temperature, a solution of 2-(4-bromo-2-chlorophenyl)ethyl iodide (246 g) of Reference Example 18 in tetrahydrofuran (940 mL) was added to the reaction mixture, and the mixture was refluxed with stirring for 15 hr. After cooling, the reaction mixture was poured into 25% aqueous citric acid solution. After partitioning and extraction with ethyl acetate, the organic layer was washed with water and 25% brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to give the title compound (227 g) as a pale-yellow oil.

후처리

  1. additionwas added
  2. temperatureAfter heating the mixture to the refluxing temperature
  3. temperaturethe mixture was refluxed
  4. temperatureAfter cooling
  5. customAfter partitioning
  6. extractionextraction with ethyl acetate
  7. washthe organic layer was washed with water and 25% brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. customThe solvent was evaporated under reduced pressure
  10. customthe residue was purified by silica gel column chromatography

출처 및 근거

ORD 기록
ord-f3f013c304cb47b3b7d2812bd2c0b21b
출처 데이터셋
uspto-grants-2012_02
특허 번호
US08114902B2

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