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

HRID 1517998

반응식

HRID 1517998 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+].C(OCC)(=O)C>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1.C(Cl)(Cl)Cl>[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

9

반응물 4

HCID 8857Ethyl AcetateHCID 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 4

HCID 521585Tris(furan-2-yl)phosphane촉매HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladium촉매HCID 6212Chloroform용매HCID 8028Tetrahydrofuran용매2회

실험 절차

Under an argon stream, 1M solution (2.9 ml, 2.9 mmol) of 2,3-dichlorobenzylzinc chloride in THF obtained in the same manner as in Reference Example 1 was added to THF (20 ml), and then bis(dibenzylideneacetone)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 hrs, and then a solution (1.0 ml, 1.0 mmol) of 2,3-dichlorobenzylzinc chloride in THF was added. The mixture was heated under reflux for 1 hr. After allowing the mixture to cool, saturated aqueous ammonium chloride solution was added to the reaction solution and insoluble materials were filtered off with Celite. The filtrate was extracted with ethyl acetate, and 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 purified by silica gel chromatography (ethyl acetate:hexane=1:1), and then by PTLC (ethyl acetate:chloroform=1:2) to give an 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. filtrationwere filtered off with 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 purified by silica gel chromatography (ethyl acetate:hexane=1:1)

출처 및 근거

ORD 기록
ord-4070a04b5cab4703835cf1fe0e9820fa
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08232401B2

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