Ammonium Chloride → Ethyl 6-(2,3-dichlorobenzyl)-1,4-dihydro-8-fluoro-1-[2-(tert-butyldimethylsilyloxy)ethyl]-4-oxo-3-quinolinecarboxylate

HRID 491523노트

반응식

HRID 491523 반응식
[F:1][C:2]1[CH:3]=[C:4](I)[CH:5]=[C:6]2[C:11]=1[N:10]([CH2:12][CH2:13][O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])[CH:9]=[C:8]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[C:7]2=[O:27].[Cl-].[Cl:30][C:31]1[C:38]([Cl:39])=[CH:37][CH:36]=[CH:35][C:32]=1[CH2:33][Zn+].[Cl-].[NH4+]>C1COCC1.O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1>[Cl:30][C:31]1[C:38]([Cl:39])=[CH:37][CH:36]=[CH:35][C:32]=1[CH2:33][C:4]1[CH:5]=[C:6]2[C:11](=[C:2]([F:1])[CH:3]=1)[N:10]([CH2:12][CH2:13][O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])[CH:9]=[C:8]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[C:7]2=[O:27]

참가 물질

6

반응물 3

HCID 25517Ammonium ChlorideHCID 23083974Ethyl 1,4-dihydro-8-fluoro-6-iodo-1-[2-(tert-butyldimethylsilyloxy)ethyl]-4-oxo-3-quinolinecarboxylateHCID 178478089HCID 178478089, 화합물

생성물 1

HCID 23083923Ethyl 6-(2,3-dichlorobenzyl)-1,4-dihydro-8-fluoro-1-[2-(tert-butyldimethylsilyloxy)ethyl]-4-oxo-3-quinolinecarboxylate수율 101.7%

시약·촉매·용매 2

HCID 521585Tris(furan-2-yl)phosphane촉매HCID 8028Tetrahydrofuran용매2회

실험 절차

Under an argon stream, the 1M THF solution (2.9 ml, 2.9 mmol) of 2,3-dichlorobenzylzinc chloride obtained in the same manner as in Reference Example 1 was added to THF (20 ml), then bis(dibenzylidenacetone)palladium(0) (22 mg, 0.039 mmol), tri(2-furyl)phosphine (18 mg, 0.077 mmol) and ethyl 1,4-dihydro-8-fluoro-6-iodo-1-[2-(tert-butyldimethylsilyloxy)ethyl]-4-oxo-3-quinolinecarboxylate (1.0 g, 1.9 mmol) obtained in Step 4 were added. The mixture was stirred at room temperature for 17 hr, a solution (1.0 ml, 1.0 mmol) of 2,3-dichlorobenzylzinc chloride in THF was further added, and the mixture was heated under reflux for 1 hr. After allowing to cool, saturated aqueous ammonium chloride solution was added to the reaction mixture, and the insoluble material was filtered through celite. The filtrate was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the obtained residue was crudely purified by silica gel chromatography (ethyl acetate:hexane=1:1) and successively purified by PTLC (ethyl acetate:chloroform=1:2) to give the object product (562 mg, yield 53%) as a pale-yellow oil.

후처리

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 1 hr
  3. temperatureto cool
  4. filtrationthe insoluble material was filtered through celite
  5. extractionThe filtrate was extracted with ethyl acetate
  6. washThe organic layer was washed with water and saturated brine
  7. dry with materialdried over sodium sulfate
  8. filtrationAfter filtration
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. customthe obtained residue was crudely purified by silica gel chromatography (ethyl acetate:hexane=1:1)
  11. customsuccessively purified by PTLC (ethyl acetate:chloroform=1:2)

출처 및 근거

ORD 기록
ord-97b426d439e2420e924e9ee8c1b1d7fa
출처 데이터셋
uspto-grants-2009_05
특허 번호
US07531554B2

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