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

HRID 70535ノート

反応式

HRID 70535 の反応式
[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]

参加物

9

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 4

HCID 83717Copper iodide触媒HCID 178418476HCID 178418476、化合物触媒HCID 6342Acetonitrile溶媒HCID 8471Triethylamine溶媒

実験手順

(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%).

後処理

  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)

出典と根拠

ORDレコード
ord-edc21bea7870426286143731e7bd8c11
出典データセット
uspto-grants-2014_09
特許番号
US08822503B2

反応ノート

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