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

HRID 70535노트

반응식

HRID 70535 반응식
[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]

참가 물질

9

반응물 4

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

생성물 1

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

시약·촉매·용매 4

HCID 83717Copper iodide촉매HCID 178418476HCID 178418476, 화합물촉매HCID 6342Acetonitrile용매HCID 8471Triethylamine용매

실험 절차

(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%).

후처리

  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)

출처 및 근거

ORD 기록
ord-edc21bea7870426286143731e7bd8c11
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08822503B2

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