Water → tert-butyl 3-(6-{(E)-1-(4-tert-butylphenyl)-2-[(2R)-1-(2,4-dimethoxybenzyl)-5-oxopyrrolidin-2-yl]ethenyl}-2-methoxypyridin-3-yl)propanoate

HRID 70667노트

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HRID 70667 반응식
[C:1]([C:5]1[CH:10]=[CH:9][C:8](/[C:11](/[Sn](CCCC)(CCCC)CCCC)=[CH:12]\[C@@H:13]2[N:17]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][C:20]=3[O:27][CH3:28])[C:16](=[O:29])[CH2:15][CH2:14]2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].Br[C:44]1[N:49]=[C:48]([O:50][CH3:51])[C:47]([CH2:52][CH2:53][C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])=[CH:46][CH:45]=1.[F-].[Cs+].O>CN(C)C=O.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.[Cu](I)I.C(OCC)(=O)C>[C:1]([C:5]1[CH:10]=[CH:9][C:8](/[C:11](/[C:44]2[N:49]=[C:48]([O:50][CH3:51])[C:47]([CH2:52][CH2:53][C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])=[CH:46][CH:45]=2)=[CH:12]\[C@H:13]2[CH2:14][CH2:15][C:16](=[O:29])[N:17]2[CH2:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][C:20]=2[O:27][CH3:28])=[CH:7][CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

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 58452887Tert-butyl 3-(6-bromo-2-methoxypyridin-3-yl)propanoate

생성물 1

HCID 67401618tert-butyl 3-(6-{(E)-1-(4-tert-butylphenyl)-2-[(2R)-1-(2,4-dimethoxybenzyl)-5-oxopyrrolidin-2-yl]ethenyl}-2-methoxypyridin-3-yl)propanoate

시약·촉매·용매 4

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

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온도
65 °C

실험 절차

Tetrakis(triphenylphosphine)palladium(0) (80 mg) was 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 (471 mg), tert-butyl 3-(6-bromo-2-methoxypyridin-3-yl)propanoate obtained in Reference Example 4-41 (436 mg), cesium fluoride (209 mg) and copper iodide (144 mg) in N,N-dimethylformamide (4.5 mL) in a nitrogen atmosphere, and the mixture was stirred at 65° C. for one hour. The reaction solution was left to cool, and then water and ethyl acetate were added, followed by filtration through celite. The filtrate was extracted with ethyl acetate. The organic layer was washed with water and brine and dried over anhydrous magnesium sulfate, after which the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1) to give tert-butyl 3-(6-{(E)-1-(4-tert-butylphenyl)-2-[(2R)-1-(2,4-dimethoxybenzyl)-5-oxopyrrolidin-2-yl]ethenyl}-2-methoxypyridin-3-yl)propanoate as a brown oil (293 mg).

후처리

  1. waitThe reaction solution was left
  2. temperatureto cool
  3. filtrationfollowed by filtration through celite
  4. extractionThe filtrate was extracted with ethyl acetate
  5. washThe organic layer was washed with water and brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customafter which the solvent was evaporated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1)

출처 및 근거

ORD 기록
ord-679629c7e31b41639236ec8a96ddb8b8
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08822503B2

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