Water → HCID 67398518, compound

HRID 70644Notes

Reaction equation

HRID 70644 reaction equation
[CH3:1][O:2][C:3]1[CH:40]=[C:39]([O:41][CH3:42])[CH:38]=[CH:37][C:4]=1[CH2:5][N:6]1[C@@H:10](/[CH:11]=[C:12](/[Sn](CCCC)(CCCC)CCCC)\[C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=2)[CH2:9][CH2:8][C:7]1=[O:36].[CH:43]1([O:48][C:49]2[C:50]([O:56][CH3:57])=[N:51][C:52](I)=[CH:53][CH:54]=2)[CH2:47][CH2:46][CH2:45][CH2:44]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>[CH:43]1([O:48][C:49]2[CH:54]=[CH:53][C:52](/[C:12](/[C:13]3[CH:14]=[CH:15][C:16]([C:19]([F:21])([F:22])[F:20])=[CH:17][CH:18]=3)=[CH:11]/[C@@H:10]3[N:6]([CH2:5][C:4]4[CH:37]=[CH:38][C:39]([O:41][CH3:42])=[CH:40][C:3]=4[O:2][CH3:1])[C:7](=[O:36])[CH2:8][CH2:9]3)=[N:51][C:50]=2[O:56][CH3:57])[CH2:44][CH2:45][CH2:46][CH2:47]1

Participants

9

Reactant 4

HCID 962WaterHCID 25953Cesium fluorideHCID 58452912HCID 58452912, compoundHCID 67396152(5R)-1-(2,4-dimethoxybenzyl)-5-{(E)-2-(tributylstannyl)-2-[4-(trifluoromethyl)phenyl]ethenyl}pyrrolidin-2-one

Product 1

HCID 67398518HCID 67398518, compound

Reagents, catalysts & solvents 4

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

Conditions

Temperature
65 °C

Procedure

Tetrakis(triphenylphosphine)palladium(0) (30 mg) was added to a solution of (5R)-1-(2,4-dimethoxybenzyl)-5-{(E)-2-(tributylstannyl)-2-[4-(trifluoromethyl)phenyl]ethenyl}pyrrolidin-2-one obtained in Reference Example 4-29 (184 mg), 3-(cyclopentyloxy)-6-iodo-2-methoxypyridine obtained in Reference Example 4-37 (169 mg), cesium fluoride (80 mg) and copper iodide (60 mg) in N,N-dimethylformamide (2 mL) in a nitrogen atmosphere, and the mixture was stirred at 65° C. for three hours. 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=19:1→1:1) to give (5R)-5-{(E)-2-[5-(cyclopentyloxy)-6-methoxypyridin-2-yl]-2-[4-(trifluoromethyl)phenyl]ethenyl}-1-(2,4-dimethoxybenzyl)pyrrolidin-2-one as a light yellow oil (184 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=19:1→1:1)

Sources & evidence

ORD record
ord-b103e04d24314ff5b55183f2c9bbb300
Source dataset
uspto-grants-2014_09
Patent number
US08822503B2

Reaction notes

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