Dimethylformamide → Methyl 2-(3-(4-fluorobenzyl)-2-oxoimidazolidin-1-yl)isonicotinate

HRID 714291ノート

反応式

HRID 714291 の反応式
[O:1]=[C:2]1[NH:6][CH2:5][CH2:4][N:3]1[C:7]1[CH:8]=[C:9]([CH:13]=[CH:14][N:15]=1)[C:10]([O-:12])=[O:11].[H-].[Na+].Br[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=1.[CH3:27]N(C)C=O>>[F:26][C:23]1[CH:24]=[CH:25][C:20]([CH2:19][N:6]2[CH2:5][CH2:4][N:3]([C:7]3[CH:8]=[C:9]([CH:13]=[CH:14][N:15]=3)[C:10]([O:12][CH3:27])=[O:11])[C:2]2=[O:1])=[CH:21][CH:22]=1

参加物

5

反応物 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 680214-Fluorobenzyl bromideHCID 866530512-(2-Oxoimidazolidin-1-yl)isonicotinate

生成物 1

HCID 58247772Methyl 2-(3-(4-fluorobenzyl)-2-oxoimidazolidin-1-yl)isonicotinate収率 67%

反応条件

温度
0 °C

実験手順

To a solution of 2-(2-oxoimidazolidin-1-yl)isonicotinate (10.00 g, 45.20 mmol) in N,N-dimethylformamide (300 mL) was added sodium hydride (60% dispersion in mineral oil, 1.90 g, 45.20 mmol) at 0° C. The resulting solution was stirred for 30 minutes at 0° C., followed by the addition of 1-(bromomethyl)-4-fluorobenzene (8.54 g, 45.20 mmol). The reaction mixture was warmed to ambient temperature, stirred for 17 hours and concentrated in vacuo to dryness. The residue was purified by column chromatography eluted with dichloromethane and ethyl acetate to give methyl 2-(3-(4-fluorobenzyl)-2-oxoimidazolidin-1-yl)isonicotinate as a colorless solid (10.03 g, 67%): mp 119-121° C.; 1H NMR (300 MHz, CDCl3) δ 8.87 (d, J=0.6 Hz, 1H), 8.35 (d, J=5.4 Hz, 1H), 7.45-7.43 (m, 1H), 7.29-7.25 (m, 2H), 7.04-6.98 (m, 2H), 4.44 (s, 2H), 4.20 (t, J=7.8 Hz, 2H), 3.91 (s, 3H), 3.35 (t, J=7.8 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 165.9, 164.0, 160.7, 156.8, 153.4, 148.0, 138.7, 132.3, 130.0, 116.7, 115.8, 115.5, 112.5, 52.6, 47.8, 41.3, 41.0; MS (ES+) m/z 330.2 (M+1).

後処理

  1. temperatureThe reaction mixture was warmed to ambient temperature
  2. stirringstirred for 17 hours
  3. concentrationconcentrated in vacuo to dryness
  4. customThe residue was purified by column chromatography
  5. washeluted with dichloromethane and ethyl acetate

出典と根拠

ORDレコード
ord-b9d62e2632b54e3b8ee6c3df05df23c4
出典データセット
uspto-grants-2015_11
特許番号
US09187426B2

反応ノート

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