Water → HCID 67398288, compound

HRID 70672Notes

Reaction equation

HRID 70672 reaction equation
[Cu]([C:4]#[N:5])C#N.Br[C:7]1[CH:8]=[CH:9][C:10](/[C:15](/[C:34]2[CH:39]=[CH:38][C:37]([C:40]([CH3:43])([CH3:42])[CH3:41])=[CH:36][CH:35]=2)=[CH:16]/[C@@H:17]2[N:21]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][C:24]=3[O:31][CH3:32])[C:20](=[O:33])[CH2:19][CH2:18]2)=[N:11][C:12]=1[O:13][CH3:14].O>CN(C)C=O>[C:40]([C:37]1[CH:36]=[CH:35][C:34](/[C:15](/[C:10]2[N:11]=[C:12]([O:13][CH3:14])[C:7]([C:4]#[N:5])=[CH:8][CH:9]=2)=[CH:16]\[C@H:17]2[CH2:18][CH2:19][C:20](=[O:33])[N:21]2[CH2:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][C:24]=2[O:31][CH3:32])=[CH:39][CH:38]=1)([CH3:43])([CH3:41])[CH3:42]

Participants

5

Reactant 3

HCID 962WaterHCID 67397955(5R)-5-[(E)-2-(5-bromo-6-methoxypyridin-2-yl)-2-(4-tert-butylphenyl)ethenyl]-1-(2,4-dimethoxybenzyl)pyrrolidin-2-oneHCID 178418260HCID 178418260, compound

Product 1

HCID 67398288HCID 67398288, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
180 °C

Procedure

Copper cyanide (27 mg) was added to a solution of (5R)-5-[(E)-2-(5-bromo-6-methoxypyridin-2-yl)-2-(4-tert-butylphenyl)ethenyl]-1-(2,4-dimethoxybenzyl)pyrrolidin-2-one obtained in Reference Example 4-42(1) (90 mg) in N,N-dimethylformamide (5 mL), and the mixture was stirred at an external temperature of 180° C. for two hours. Water was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with saline, dried over magnesium sulfate and filtered. The solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1→1:1) to give 6-{(E)-1-(4-tert-butylphenyl)-2-[(2R)-1-(2,4-dimethoxybenzyl)-5-oxopyrrolidin-2-yl]ethenyl}-2-methoxypyridine-3-carbonitrile (32 mg, 40%).

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe organic layer was washed with saline
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. customThe solvent was then evaporated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1→1:1)

Sources & evidence

ORD record
ord-95f52f784d4e4b609a39ee1cd0d71c4b
Source dataset
uspto-grants-2014_09
Patent number
US08822503B2

Reaction notes

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