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Water → (5R)-5-{(E)-2-(5-chloro-6-methoxypyridin-2-yl)-2-[4-(propan-2-yl)phenyl]ethenyl}-1-(2,4-dimethoxybenzyl)pyrrolidin-2-one

HRID 70637
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인쇄 미리보기

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HRID 70637 반응식
Br[C:2]1[N:7]=[C:6]([O:8][CH3:9])[C:5]([Cl:10])=[CH:4][CH:3]=1.[F-].[Cs+].[CH3:13][O:14][C:15]1[CH:51]=[C:50]([O:52][CH3:53])[CH:49]=[CH:48][C:16]=1[CH2:17][N:18]1[C@@H:22](/[CH:23]=[C:24](\[C:38]2[CH:43]=[CH:42][C:41]([CH:44]([CH3:46])[CH3:45])=[CH:40][CH:39]=2)/[Sn](CCCC)(CCCC)CCCC)[CH2:21][CH2:20][C:19]1=[O:47].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>[Cl:10][C:5]1[CH:4]=[CH:3][C:2](/[C:24](/[C:38]2[CH:39]=[CH:40][C:41]([CH:44]([CH3:46])[CH3:45])=[CH:42][CH:43]=2)=[CH:23]/[C@@H:22]2[N:18]([CH2:17][C:16]3[CH:48]=[CH:49][C:50]([O:52][CH3:53])=[CH:51][C:15]=3[O:14][CH3:13])[C:19](=[O:47])[CH2:20][CH2:21]2)=[N:7][C:6]=1[O:8][CH3:9]
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참가 물질

9

반응물 4

HCID 962WaterHCID 25953Cesium fluorideHCID 58452258(5R)-1-(2,4-dimethoxybenzyl)-5-[(E)-2-[4-(propan-2-yl)phenyl]-2-(tributylstannyl)ethenyl]pyrrolidin-2-oneHCID 584523026-Bromo-3-chloro-2-methoxypyridine

생성물 1

HCID 67397494(5R)-5-{(E)-2-(5-chloro-6-methoxypyridin-2-yl)-2-[4-(propan-2-yl)phenyl]ethenyl}-1-(2,4-dimethoxybenzyl)pyrrolidin-2-one

시약·촉매·용매 4

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

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온도
65 °C

실험 절차

6-bromo-3-chloro-2-methoxypyridine (361 mg), cesium fluoride (246 mg), copper iodide (170 mg) and tetrakis(triphenylphosphine)palladium(0) (92 mg) were added to a solution of (5R)-1-(2,4-dimethoxybenzyl)-5-[(E)-2-[4-(propan-2-yl)phenyl]-2-(tributylstannyl)ethenyl]pyrrolidin-2-one obtained in Reference Example 4-27 (543 mg) in N,N-dimethylformamide (6 mL), and the mixture was stirred at 65° C. for 1.5 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=4:1→0:1) to give (5R)-5-{(E)-2-(5-chloro-6-methoxypyridin-2-yl)-2-[4-(propan-2-yl)phenyl]ethenyl}-1-(2,4-dimethoxybenzyl)pyrrolidin-2-one as a yellow oil (268 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=4:1→0:1)

출처 및 근거

ORD 기록
ord-5d0cd933178c4fa0b238c6c3fefe6439
출처 데이터셋
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08822503B2

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