Methyl acetoacetate → Methyl 5-Methyl-3-(4-pyridyl)isoxazole-4-carboxylate

HRID 1828853ノート

反応式

HRID 1828853 の反応式
[Na].[C:2]([O:8][CH3:9])(=[O:7])[CH2:3][C:4]([CH3:6])=[O:5].O[N:11]=[C:12](Cl)[C:13]1[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=1>CO>[CH3:6][C:4]1[O:5][N:11]=[C:12]([C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)[C:3]=1[C:2]([O:8][CH3:9])=[O:7]

参加物

5

反応物 3

HCID 7757Methyl acetoacetateHCID 3014266N-hydroxy-4-pyridine-carboximidoyl chlorideHCID 5360545Sodium

生成物 1

HCID 82127276Methyl 5-Methyl-3-(4-pyridyl)isoxazole-4-carboxylate収率 43%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

反応条件

温度
0 °C

実験手順

Sodium (0.400 g, 0.0166 mol) was added to anhydrous methanol under nitrogen. After complete dissolution, the reaction vessel was cooled to 0° C. and methyl acetoacetate (1.8 ml, 0.166 mol) added. A solution of N-hydroxy-4-pyridine carboximidoyl chloride (2 g, 0.0128 mol; prepared according to Kocevar, M., Synth. Commun., 1988, 18(12), 1427) was added dropwise over 20 minutes. The reaction was stirred at 25° C. for 16 h, and quenched with acetic acid (1 ml). The methanol was removed in vacuo and the product partitioned between EtOAc and water. The organic layer was collected, dried over MgSO4, and evaporated. The residue was chromatographed on silica eluting with 20% EtOAc/hexane→EtOAc to obtain the title compound as a beige solid (1.2 g). 1H NMR (400 MHz, CDCl3) δ 8.73–8.71 (m, 2H), 7.57–7.56 (m, 2H), 3.80 (s, 3H), 2.77(s, 3H).

後処理

  1. dissolutionAfter complete dissolution
  2. customquenched with acetic acid (1 ml)
  3. customThe methanol was removed in vacuo
  4. customthe product partitioned between EtOAc and water
  5. customThe organic layer was collected
  6. dry with materialdried over MgSO4
  7. customevaporated
  8. customThe residue was chromatographed on silica eluting with 20% EtOAc/hexane

出典と根拠

ORDレコード
ord-3d66b4bfa1ea41539c237744f3495c67
出典データセット
uspto-grants-2006_06
特許番号
US07060710B2

反応ノート

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