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Tetrahydrofuran → 1-[5-(4-Fluoro-phenylethynyl)-pyridin-2-yl]-4,4-dimethyl-pyrrolidin-2-one

HRID 1894248
ノート
印刷プレビュー

反応式

HRID 1894248 の反応式
[CH3:1][C:2]1([CH3:20])[CH2:6][N:5]([C:7]2[N:12]=[CH:11][C:10]([C:13]#[C:14][Si](C)(C)C)=[CH:9]N=2)[C:4](=[O:19])[CH2:3]1.[F:21][C:22]1[CH:27]=[CH:26][C:25](I)=[CH:24][CH:23]=1.[CH3:29]CN(CC)CC.CCCC[N+](CCCC)(CCCC)CCCC.[F-].C1COCC1>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Cu]I>[F:21][C:22]1[CH:27]=[CH:26][C:25]([C:14]#[C:13][C:10]2[CH:9]=[CH:29][C:7]([N:5]3[CH2:6][C:2]([CH3:1])([CH3:20])[CH2:3][C:4]3=[O:19])=[N:12][CH:11]=2)=[CH:24][CH:23]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

9

反応物 5

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 96054-FluoroiodobenzeneHCID 2724141Tetrabutylammonium FluorideHCID 584641394,4-Dimethyl-1-(5-trimethylsilanylethynyl-pyrimidin-2-yl)-pyrrolidin-2-one

生成物 1

HCID 575167621-[5-(4-Fluoro-phenylethynyl)-pyridin-2-yl]-4,4-dimethyl-pyrrolidin-2-one
収率 77.8%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 6102075Dichlorobis(triphenylphosphine)palladium触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
70 °C

実験手順

4,4-Dimethyl-1-(5-trimethylsilanylethynyl-pyrimidin-2-yl)-pyrrolidin-2-one (Example 120, step 2) (30 mg, 0.1 mmol) was dissolved in DMF (1 ml). 1-Fluoro-4-iodobenzene (32 mg, 0.14 mmol, 1.4 equiv.), Et3N (43 μl, 0.31 mmol, 3 equiv.), Bis-(triphenylphosphine)-palladium(II)dichloride (4 mg, 5.2 μmol, 0.05 equiv.) and copper(I)iodide (0.6 mg, 3.1 μmol, 0.03 equiv.) were added under nitrogen and the mixture was heated to 70° C. TBAF 1M in THF (115 μl, 0.115 mmol, 1.1 equiv.) was added dropwise in 20 minutes at 70° C. The reaction mixture was stirred for 30 minutes at 70° C. and evaporated with isolute to dryness. The crude product was purified by flash chromatography with a 20 g silica gel column and eluting with heptane:ethyl acetate 100:0→0:100. The desired 1-[5-(4-fluoro-phenylethynyl)-pyridin-2-yl]-4,4-dimethyl-pyrrolidin-2-one (24 mg, 73% yield) was obtained as a white solid, MS: m/e=310.1 (M+H+).

後処理

  1. customevaporated with isolute to dryness
  2. customThe crude product was purified by flash chromatography with a 20 g silica gel column
  3. washeluting with heptane:ethyl acetate 100:0→0:100

出典と根拠

ORDレコード
ord-b6c16f8120014f2d97e67aa8f52e30ce
出典データセット
uspto-grants-2013_08
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08513273B2

反応ノート

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