Water → (5R)-5-[(5-Chloro-6-methoxypyridin-2-yl)ethynyl]-1-(2,4-dimethoxybenzyl)pyrrolidin-2-one

HRID 70535Notes

Reaction equation

HRID 70535 reaction equation
[CH3:1][O:2][C:3]1[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[CH:14][C:4]=1[CH2:5][N:6]1[C@@H:10]([C:11]#[CH:12])[CH2:9][CH2:8][C:7]1=[O:13].Cl.N[C@@H](C(OC)=O)CCC(OC)=O.Br[C:34]1[N:39]=[C:38]([O:40][CH3:41])[C:37]([Cl:42])=[CH:36][CH:35]=1.O>C(#N)C.C(N(CC)CC)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu](I)I>[Cl:42][C:37]1[CH:36]=[CH:35][C:34]([C:12]#[C:11][C@@H:10]2[N:6]([CH2:5][C:4]3[CH:14]=[CH:15][C:16]([O:18][CH3:19])=[CH:17][C:3]=3[O:2][CH3:1])[C:7](=[O:13])[CH2:8][CH2:9]2)=[N:39][C:38]=1[O:40][CH3:41]

Participants

9

Reactant 4

HCID 962WaterHCID 12917567Dimethyl D-glutamate hydrochlorideHCID 584523026-Bromo-3-chloro-2-methoxypyridineHCID 58452699(5R)-1-(2,4-Dimethoxybenzyl)-5-ethynylpyrrolidin-2-one

Product 1

HCID 58452822(5R)-5-[(5-Chloro-6-methoxypyridin-2-yl)ethynyl]-1-(2,4-dimethoxybenzyl)pyrrolidin-2-oneYield 52%

Reagents, catalysts & solvents 4

HCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolventHCID 8471TriethylamineSolvent

Procedure

(5R)-1-(2,4-Dimethoxybenzyl)-5-ethynylpyrrolidin-2-one (600 mg, synthesized according to Tetrahedron Asymmetry, 1995, 239 using dimethyl (R)-glutamate hydrochloride as a raw material) in acetonitrile (6 mL) was added to a solution of 6-bromo-3-chloro-2-methoxypyridine (667 mg), bis(triphenylphosphine)palladium(II) dichloride (81 mg) and copper iodide (22 mg) in triethylamine (12 mL) in a nitrogen gas stream at 40° C. over 30 minutes. The mixture was stirred at room temperature for four hours. The reaction solution was poured into water, followed by extraction with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and filtered. The solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1→0:1) to give the title compound as a colorless oil (452 mg, 52%).

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous 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=1:1→0:1)

Sources & evidence

ORD record
ord-edc21bea7870426286143731e7bd8c11
Source dataset
uspto-grants-2014_09
Patent number
US08822503B2

Reaction notes

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