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Sodium Carbonate → Ethyl 1-cyclopropyl-8-(difluoromethoxy)-7-[(1R)-2,3-dihydro-1-methyl-2-(triphenylmethyl)-1H-isoindol-5-yl]-1,4-dihydro-4-oxo-3-quinolinecarboxylate

HRID 1018530
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인쇄 미리보기

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HRID 1018530 반응식
[CH3:1][C@@H:2]1[C:10]2[C:5](=[CH:6][C:7](B3OCCNCCO3)=[CH:8][CH:9]=2)[CH2:4][N:3]1[C:19]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.Br[C:39]1[C:48]([O:49][CH:50]([F:52])[F:51])=[C:47]2[C:42]([C:43](=[O:61])[C:44]([C:56]([O:58][CH2:59][CH3:60])=[O:57])=[CH:45][N:46]2[CH:53]2[CH2:55][CH2:54]2)=[CH:41][CH:40]=1.C(=O)([O-])[O-].[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O.C(Cl)Cl.C(OCC)(=O)C>[CH:53]1([N:46]2[C:47]3[C:42](=[CH:41][CH:40]=[C:39]([C:7]4[CH:6]=[C:5]5[C:10](=[CH:9][CH:8]=4)[C@@H:2]([CH3:1])[N:3]([C:19]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)([C:26]4[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=4)[C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[CH2:4]5)[C:48]=3[O:49][CH:50]([F:52])[F:51])[C:43](=[O:61])[C:44]([C:56]([O:58][CH2:59][CH3:60])=[O:57])=[CH:45]2)[CH2:55][CH2:54]1
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참가 물질

8

반응물 3

HCID 10340Sodium CarbonateHCID 104131955-(1,3,6,2-Dioxazaborocan-2-yl)-1-methyl-2-(triphenylmethyl)-2,3-dihydro-1H-isoindoleHCID 11732152Ethyl 7-bromo-1-cyclopropyl-8-(difluoromethoxy)-4-oxo-1,4-dihydro-3-quinolinecarboxylate

생성물 1

HCID 15887919Ethyl 1-cyclopropyl-8-(difluoromethoxy)-7-[(1R)-2,3-dihydro-1-methyl-2-(triphenylmethyl)-1H-isoindol-5-yl]-1,4-dihydro-4-oxo-3-quinolinecarboxylate수율 89.5%

시약·촉매·용매 4

HCID 178418476HCID 178418476, 화합물촉매HCID 962Water용매2회HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

실험 절차

In a mixed solvent of 2 ml of water and 5 ml of ethyl acetate is suspended 1.34 g of 2-[(1R)-1-methyl-2-trityl-2,3-dihydro-1H-5-isoindolyl]-1,3,6,2-dioxazaborocane and to this suspension are added 1.0 g of ethyl 7-bromo-1-cyclopropyl-8-difluoromethoxy-1,4-dihydro-4-oxoquinoline-3-carboxylate, 0.55 g of sodium carbonate and 0.05 g of bis(triphenylphosphine)palladium(II) chloride, after which the resulting mixture is heated under reflux for 3 hours in a nitrogen atmosphere. The reaction mixture is added to a mixed solvent of 10 ml of methylene chloride and 10 ml of water and the organic layer is separated. The organic layer obtained is washed with saturated saline and then dried over anhydrous magnesium sulfate, after which the solvent is removed from the layer by distillation under reduced pressure. The residue obtained is recrystallized from ethanol to obtain 1.55 g of ethyl 1-cyclopropyl-8-difluoromethoxy-7-[(1R)-1-methyl-2-trityl-2,3-dihydro-1H-5-isoindolyl]-4-oxo-1,4-dihydro-3-quinolinecarboxylate.

후처리

  1. temperatureafter which the resulting mixture is heated
  2. temperatureunder reflux for 3 hours in a nitrogen atmosphere
  3. customthe organic layer is separated
  4. customThe organic layer obtained
  5. washis washed with saturated saline
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customafter which the solvent is removed from the layer by distillation under reduced pressure
  8. customThe residue obtained
  9. customis recrystallized from ethanol

출처 및 근거

ORD 기록
ord-7371748fc3344e5b98604a11dfaf1654
출처 데이터셋
uspto-grants-2002_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US06482835B2

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