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

HRID 1828853Notes

Reaction equation

[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]

Participants

Conditions

Temperature: 0 °C

Procedure

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).

Workup

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

Sources & evidence

ORD record: ord-3d66b4bfa1ea41539c237744f3495c67
Source dataset: uspto-grants-2006_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07060710B2

Reaction notes

Loading…