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

HRID 1828853노트

반응식

HRID 1828853 반응식
[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]

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 887Methanol용매

반응 조건

온도
0 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-3d66b4bfa1ea41539c237744f3495c67
출처 데이터셋
uspto-grants-2006_06
특허 번호
US07060710B2

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