Sodium hydride → Methyl 2-(3-(cyclopropylmethyl)-2-oxoimidazolidin-1-yl)thiazole-5-carboxylate

HRID 560786ノート

反応式

HRID 560786 の反応式
[O:1]=[C:2]1[NH:6][CH2:5][CH2:4][N:3]1[C:7]1[S:8][C:9]([C:12]([O:14][CH3:15])=[O:13])=[CH:10][N:11]=1.[H-].[Na+].Br[CH2:19][CH:20]1[CH2:22][CH2:21]1>CN(C)C=O.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH:20]1([CH2:19][N:6]2[CH2:5][CH2:4][N:3]([C:7]3[S:8][C:9]([C:12]([O:14][CH3:15])=[O:13])=[CH:10][N:11]=3)[C:2]2=[O:1])[CH2:22][CH2:21]1

参加物

6

反応物 3

HCID 24758Sodium hydrideHCID 81503BromomethylcyclopropaneHCID 58031476Methyl 2-(2-oxoimidazolidin-1-yl)thiazole-5-carboxylate

生成物 1

HCID 58031461Methyl 2-(3-(cyclopropylmethyl)-2-oxoimidazolidin-1-yl)thiazole-5-carboxylate収率 24%

試薬・触媒・溶媒 2

HCID 67553Tetrabutylammonium Iodide触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

To a solution of methyl 2-(2-oxoimidazolidin-1-yl)thiazole-5-carboxylate (0.50 g, 2.20 mmol) in N,N-dimethylformamide (15 mL) was added sodium hydride (0.084 g, 3.52 mmol, 60% in mineral oil) at 0° C. The reaction mixture was stirred at 0° C. for 0.5 hours, followed by the addition of (bromomethyl)cyclopropane (0.36 g, 2.64 mmol) and catalytic amount of tetra-n-butylammonium iodide. The reaction mixture was stirred at ambient temperature for 20 hours. The solvent was concentrated in vacuo, then diluted with ethyl acetate (200 mL) and washed with water (150 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluted with ethyl acetate/hexane (2/3) to afford the title compound as a colorless solid in 24% yield (0.15 g): mp 124-126° C. (ethyl acetate/hexanes); 1H NMR (300 MHz, CDCl3) δ 8.01 (s, 1H), 4.15-4.10 (m, 2H), 3.83 (s 3H), 3.73-3.68 (m, 2H) 3.20 (d, J=7.1 Hz, 2H), 0.97-0.92 (m, 1H), 0.61-0.53 (m, 2H), 0.30-0.20 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 163.4, 162.6, 155.0, 145.2, 121.6, 52.0, 48.6, 42.2, 42.1, 8.9, 3.4; MS (ES+) m/z 282.2 (M+1).

後処理

  1. stirringThe reaction mixture was stirred at ambient temperature for 20 hours
  2. concentrationThe solvent was concentrated in vacuo
  3. additiondiluted with ethyl acetate (200 mL)
  4. washwashed with water (150 mL)
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography
  9. washeluted with ethyl acetate/hexane (2/3)

出典と根拠

ORDレコード
ord-30268f9915eb4032bb035ad96e3469ab
出典データセット
uspto-grants-2011_11
特許番号
US08063084B2

反応ノート

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