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Water → (5R)-5-[(E)-2-(4-tert-butylphenyl)-2-{5-(difluoromethoxy)-6-[(4-methoxybenzyl)oxy]-pyridin-2-yl}ethenyl]-1-(2,4-dimethoxybenzyl)pyrrolidin-2-one

HRID 70642
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인쇄 미리보기

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HRID 70642 반응식
[F:1][CH:2]([F:21])[O:3][C:4]1[C:5]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)=[N:6][C:7](I)=[CH:8][CH:9]=1.[F-].[Cs+].[C:24]([C:28]1[CH:33]=[CH:32][C:31](/[C:34](/[Sn](CCCC)(CCCC)CCCC)=[CH:35]\[C@@H:36]2[N:40]([CH2:41][C:42]3[CH:47]=[CH:46][C:45]([O:48][CH3:49])=[CH:44][C:43]=3[O:50][CH3:51])[C:39](=[O:52])[CH2:38][CH2:37]2)=[CH:30][CH:29]=1)([CH3:27])([CH3:26])[CH3:25].O>CN(C)C=O.[Cu](I)I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(OCC)(=O)C>[C:24]([C:28]1[CH:33]=[CH:32][C:31](/[C:34](/[C:7]2[CH:8]=[CH:9][C:4]([O:3][CH:2]([F:21])[F:1])=[C:5]([O:11][CH2:12][C:13]3[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=3)[N:6]=2)=[CH:35]\[C@@H:36]2[N:40]([CH2:41][C:42]3[CH:47]=[CH:46][C:45]([O:48][CH3:49])=[CH:44][C:43]=3[O:50][CH3:51])[C:39](=[O:52])[CH2:38][CH2:37]2)=[CH:30][CH:29]=1)([CH3:27])([CH3:25])[CH3:26]
참가 물질반응 조건실험 절차후처리출처 및 근거반응 노트

참가 물질

9

반응물 4

HCID 962WaterHCID 25953Cesium fluorideHCID 58452240(5R)-5-[(E)-2-(4-tert-Butylphenyl)-2-(tributylstannyl)ethenyl]-1-(2,4-dimethoxybenzyl)pyrrolidin-2-oneHCID 584523743-(Difluoromethoxy)-6-iodo-2-[(4-methoxybenzyl)oxy]pyridine

생성물 1

HCID 67400919(5R)-5-[(E)-2-(4-tert-butylphenyl)-2-{5-(difluoromethoxy)-6-[(4-methoxybenzyl)oxy]-pyridin-2-yl}ethenyl]-1-(2,4-dimethoxybenzyl)pyrrolidin-2-one

시약·촉매·용매 4

HCID 83717Copper iodide촉매HCID 178418397HCID 178418397, 화합물촉매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

반응 조건

온도
75 °C

실험 절차

3-(Difluoromethoxy)-6-iodo-2-[(4-methoxybenzyl)oxy]pyridine obtained in Reference Example 4-34 (727 mg), cesium fluoride (270 mg), copper iodide (187 mg) and tetrakis(triphenylphosphine)palladium (103 mg) were added to a solution of (5R)-5-[(E)-2-(4-tert-butylphenyl)-2-(tributylstannyl)ethenyl]-1-(2,4-dimethoxybenzyl)pyrrolidin-2-one obtained in Reference Example 4-26 (609 mg) in N,N-dimethylformamide (6 mL), and the mixture was stirred at 75° C. for two hours. Water and ethyl acetate were added to the reaction solution. After filtration through celite, the organic layer was washed with brine. The organic layer dried over anhydrous magnesium sulfate and filtered, after which the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=95:5→1:1) to give (5R)-5-[(E)-2-(4-tert-butylphenyl)-2-{5-(difluoromethoxy)-6-[(4-methoxybenzyl)oxy]-pyridin-2-yl}ethenyl]-1-(2,4-dimethoxybenzyl)pyrrolidin-2-one as a colorless gum (511 mg).

후처리

  1. filtrationAfter filtration through celite
  2. washthe organic layer was washed with brine
  3. dry with materialThe organic layer dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. customafter which the solvent was evaporated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=95:5→1:1)

출처 및 근거

ORD 기록
ord-eb2768dfdc9c440abb4cf0271bdbf998
출처 데이터셋
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08822503B2

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