Method for preparing spiro beta-lactam
A lactam and spiro ring technology, which is applied in the field of pharmaceutical chemical synthesis, can solve the problems of few synthesis methods of β-lactam and the inability to realize one-step synthesis, and achieve the effects of high yield, easy operation, and cheap and easy-to-obtain raw materials
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Embodiment 1
[0049] Synthesis of aryl substituted methyl benzoylformate
[0050]
[0051] Add selenium dioxide (2eq) and ketoester (1eq) to pyridine (1.0M) at room temperature, stir at 110°C for 20h, filter with suction, and wash with dichloromethane. The filtrate was spin-dried and DMF (0.6M) was added, followed by potassium carbonate (3.0eq) and potassium iodide (3.0eq). Stir at room temperature for 2h. Quenched with 1N HCl and extracted with ether. Then washed with saturated sodium bicarbonate solution, washed with 10% sodium thiosulfate solution, dried over anhydrous sodium sulfate, spin-dried, and passed through the column.
Embodiment 2
[0053] Synthesis of β-lactam
[0054]
[0055] Synthesis of Compound I: Aldehyde (1eq) and methyl acrylate (3eq) were dissolved in Dioxane / H 2 O(1:1) in 0.1ml, reacted, detected by TLC, until the raw materials were basically consumed, extracted with ether, dried over anhydrous sodium sulfate, and passed through the column. Compound I was obtained.
[0056] Synthesis of Compound II: Dissolve the ester (1 mmol) in anhydrous dichloromethane (0.5 M), add DMAP (0.1 mmol) thereto, add acetic anhydride (1.6 mmol) dropwise, and stir the reaction mixture at room temperature 12h, add aqueous sodium bicarbonate solution (1v:1v), stir for 10min, separate the organic layer, dry over anhydrous sodium sulfate, and concentrate under reduced pressure to obtain compound II.
[0057] Synthesis of Compound III: Compound II (5 mmol) was dissolved in THF (8 ml), then DABCO (5 mmol) was added. Stir at room temperature for 15 min, then add amine (5 mmmol) and stir for 1 h. TLC detection. The ...
Embodiment 3
[0061]
[0062] The synthesized lactam (V, 0.1 mmol) and benzoylformate (1b, 0.2 mmol) were added to a 10 ml reaction tube, and then 1 ml THF and 0.2 mmol of tridimethylaminophosphine reagent were added thereto. Under the protection of nitrogen, react at room temperature for 30 min, and detect by TLC until the reaction is complete. Then it was spin-dried and passed through the column to obtain compound 3a: 33mg, White solid. 1 H NMR (600MHz, CDCl 3 )δ7.48(d,J=7.6Hz,2H),7.41(t,J=7.3Hz,2H),7.37-7.35(m,3H),7.34-7.32(m,3H),7.30(d,J =7.9Hz,2H),7.23(t,J=7.8Hz,2H),7.03(t,J=7.5Hz,1H),5.34(s,1H),3.71(s,3H),2.07(d,J = 5.5Hz, 1H), 1.63 (d, J = 5.7Hz, 1H).
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