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 70667Notes

Reaction equation

HRID 70667 reaction equation
[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]

Participants

9

Reactant 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

Product 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

Reagents, catalysts & solvents 4

HCID 83717Copper iodideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-679629c7e31b41639236ec8a96ddb8b8
Source dataset
uspto-grants-2014_09
Patent number
US08822503B2

Reaction notes

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