Water → (5R)-5-{(E)-2-(4-tert-butylphenyl)-2-[6-methoxy-5-(methylsulfanyl)pyridin-2-yl]ethenyl}-1-(2,4-dimethoxybenzyl)pyrrolidin-2-one

HRID 70677Notes

Reaction equation

HRID 70677 reaction equation
[CH3:1][S-:2].[Na+].Br[C:5]1[CH:6]=[CH:7][C:8](/[C:13](/[C:32]2[CH:37]=[CH:36][C:35]([C:38]([CH3:41])([CH3:40])[CH3:39])=[CH:34][CH:33]=2)=[CH:14]/[C@@H:15]2[N:19]([CH2:20][C:21]3[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][C:22]=3[O:29][CH3:30])[C:18](=[O:31])[CH2:17][CH2:16]2)=[N:9][C:10]=1[O:11][CH3:12].O>CN(C)C=O>[C:38]([C:35]1[CH:36]=[CH:37][C:32](/[C:13](/[C:8]2[CH:7]=[CH:6][C:5]([S:2][CH3:1])=[C:10]([O:11][CH3:12])[N:9]=2)=[CH:14]\[C@@H:15]2[N:19]([CH2:20][C:21]3[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][C:22]=3[O:29][CH3:30])[C:18](=[O:31])[CH2:17][CH2:16]2)=[CH:33][CH:34]=1)([CH3:41])([CH3:40])[CH3:39]

Participants

5

Reactant 3

HCID 962WaterHCID 4378561Sodium methanethiolateHCID 67397955(5R)-5-[(E)-2-(5-bromo-6-methoxypyridin-2-yl)-2-(4-tert-butylphenyl)ethenyl]-1-(2,4-dimethoxybenzyl)pyrrolidin-2-one

Product 1

HCID 67400637(5R)-5-{(E)-2-(4-tert-butylphenyl)-2-[6-methoxy-5-(methylsulfanyl)pyridin-2-yl]ethenyl}-1-(2,4-dimethoxybenzyl)pyrrolidin-2-oneYield 34%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium thiomethoxide (44 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) (150 mg) in N,N-dimethylformamide (1.5 mL), and the mixture was stirred at room temperature for 20 hours. Water was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with water and brine, 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=9:1→0:10) to give (5R)-5-{(E)-2-(4-tert-butylphenyl)-2-[6-methoxy-5-(methylsulfanyl)pyridin-2-yl]ethenyl}-1-(2,4-dimethoxybenzyl)pyrrolidin-2-one as a colorless oil (53 mg, 34%).

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe organic layer was washed with water and brine
  3. dry with materialdried 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=9:1→0:10)

Sources & evidence

ORD record
ord-4dcc96fce3d94b5a97b7b5d6448e8c3b
Source dataset
uspto-grants-2014_09
Patent number
US08822503B2

Reaction notes

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