Synthetic method of avibactam intermediate
A synthetic method and intermediate technology, which is applied in the field of synthesis of avibactam intermediates, can solve the problems of cumbersome routes, relatively expensive, and no absolute configuration of compounds, etc., and achieve the effect of mild reaction conditions and simple operation
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[0036] The invention provides a kind of synthetic method of avibactam intermediate, comprising steps:
[0037] (1) Under the protection of an inert gas, dissolve the compound (II) in the first solvent to obtain the first mixed solution, add alkali to the first mixed solution, and undergo ring closure at -78 to 110°C Reaction, the reaction reaction time is 1~72h, and compound (Ⅲ) is obtained;
[0038] (2) Dissolving the compound (III) in a second solvent to obtain a second mixed solution, adding an acid to the second mixed solution, and a decarbonylation protection reaction occurs at an environment of 20-110° C., reaction 1~ 72h, obtained compound (Ⅳ);
[0039] (3) Dissolving the compound (IV) in a third solvent to obtain a third mixed solution, adding a reducing agent to the third mixed solution, and a carbonyl reduction reaction occurs at 0-50° C. 10h, compound (I) was obtained;
[0040] The synthetic route of compound (I) is as follows:
[0041]
[0042] in:
[0043]...
Embodiment 1
[0057] Preparation of Compound (Ⅲ)
[0058] Under the protection of argon, 4.0 g of (S)-methyl 6-bromo-2-((tert-butoxycarbonyl)amino)-5,5-dimethoxyhexanoate was dissolved in 25 mL of dry tetrahydrofuran, At 0°C, 5 batches of 100 mg each were added with 500 mg of sodium hydride in total, and the reaction was carried out at room temperature for 12 h. The reaction was detected by TLC, and 40 mL of water was slowly added at 0°C to quench the reaction, and the aqueous layer was extracted 4 times with dichloromethane, each time 40 mL of dichloromethane, and the combined organic phase was washed once with 50 mL of saturated aqueous sodium bicarbonate solution, and anhydrous magnesium sulfate After drying, the solvent was spin-off and the light yellow oil obtained by separation with a silica gel column was compound (Ⅲ) (65% yield).
[0059] figure 1 is compound (Ⅲ) hydrogen spectrogram; figure 2 It is the carbon spectrum of compound (Ⅲ).
[0060] 1 H NMR (400MHz, Chloroform-d) δ...
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