Water → HCID 67398036, compound

HRID 70639Notes

Reaction equation

HRID 70639 reaction equation
I[C:2]1[N:7]=[C:6]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=2)[C:5]([O:18][CH3:19])=[CH:4][CH:3]=1.[F-].[Cs+].[C:22]([C:26]1[CH:31]=[CH:30][C:29](/[C:32](/[Sn](CCCC)(CCCC)CCCC)=[CH:33]\[C@@H:34]2[N:38]([CH2:39][C:40]3[CH:45]=[CH:44][C:43]([O:46][CH3:47])=[CH:42][C:41]=3[O:48][CH3:49])[C:37](=[O:50])[CH2:36][CH2:35]2)=[CH:28][CH:27]=1)([CH3:25])([CH3:24])[CH3:23].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:22]([C:26]1[CH:31]=[CH:30][C:29](/[C:32](/[C:2]2[CH:3]=[CH:4][C:5]([O:18][CH3:19])=[C:6]([O:8][CH2:9][C:10]3[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=3)[N:7]=2)=[CH:33]\[C@@H:34]2[N:38]([CH2:39][C:40]3[CH:45]=[CH:44][C:43]([O:46][CH3:47])=[CH:42][C:41]=3[O:48][CH3:49])[C:37](=[O:50])[CH2:36][CH2:35]2)=[CH:28][CH:27]=1)([CH3:25])([CH3:23])[CH3:24]

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 58452718HCID 58452718, compound

Product 1

HCID 67398036HCID 67398036, compound

Reagents, catalysts & solvents 4

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

Conditions

Temperature
65 °C

Procedure

6-Iodo-3-methoxy-2-[(4-methoxybenzyl)oxy]pyridine obtained in Reference Example 4-33 (657 mg), cesium fluoride (269 mg), copper iodide (185 mg) and tetrakis(triphenylphosphine)palladium(0) (102 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 (604 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=3:1→1:1) to give (5R)-5-[(E)-2-(4-tert-butylphenyl)-2-{5-methoxy-6-[(4-methoxybenzyl)oxy]-pyridin-2-yl}ethenyl]-1-(2,4-dimethoxybenzyl)pyrrolidin-2-one as a yellow oil (449 mg).

Workup

  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=3:1→1:1)

Sources & evidence

ORD record
ord-c709a740c6ab4421bba86808bb9bc785
Source dataset
uspto-grants-2014_09
Patent number
US08822503B2

Reaction notes

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