2-oxopyrrolidine derivative, preparation method thereof and preparation method of intermediate
A technology of oxypyrrolidine and derivatives, which is applied in the preparation of carbamate derivatives, the preparation of organic compounds, the preparation of cyanide reactions, etc., can solve the problems of low efficiency of 2-oxypyrrolidine derivatives and the like
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[0037] In the first typical embodiment of the present application, a preparation method of 2-oxopyrrolidine derivatives is provided, and the 2-oxopyrrolidine derivatives include L-2-oxopyrrolidine derivatives shown in formula IX or D-2-oxypyrrolidine derivatives shown in formula X; the preparation method comprises: a) carrying out α-alkylation reaction with five-membered sulfonamide and glutamic acid ester compound to generate sulfonic acid intermediate, and sulfonic acid The intermediate is subjected to an acidic hydrolysis reaction to generate an amino-protected intermediate; or an aziridine and a glutamate compound are subjected to an α-alkylation reaction to generate an amino-protected intermediate; wherein, the structural formula of the five-membered sulfonamide is formula I , the structural formula of aziridine is formula VIII; the glutamate compound is the L-glutamate compound shown in formula II or the D-glutamate compound shown in formula III, correspondingly, the sulf...
Embodiment 1
[0087]
[0088] step 1:
[0089] Compound 1 (20.0 g, 1.0 eq), THF (200 mL) were added to the reaction flask, and the temperature was lowered to -78°C. Add LDA (1.0M in THF, 160mL, 2.2eq) dropwise, and stir for 15-30min after the drop is complete. Then a THF (200 mL) solution of compound 8 (20.56 g, 1.1 eq, synthesized by reference Org. Lett., 2017, 19, 1974) was added dropwise, and the mixture was incubated and stirred for 40 min. TLC monitored that the reaction was complete (the product obtained at this time was 10A), and 20% citric acid aqueous solution (200 mL) was added dropwise to quench the reaction, warmed to room temperature, and stirred for 3-4 h. TLC detected that the intermediate reaction was complete, and compound 10 was obtained. EtOAc (200 mL) was added for separation, the organic phase was dried over sodium sulfate, filtered, concentrated, and the crude product was purified by column chromatography to obtain compound 10 as a colorless oil, 25.6 g, yield 78%....
Embodiment 2
[0098]
[0099] step 1:
[0100] Compound 1 (20.0 g, 1.0 eq), THF (200 mL) were added to the reaction flask, and the temperature was lowered to -78°C. LiHMDS (1.0M in THF, 160mL, 2.2eq) was added dropwise, and the mixture was stirred for 15-30min. Then a THF (100 mL) solution of compound 9 (15.45 g, 1.2 eq, synthesized by reference Journal of the Chemical Society. Perkin transactions I, 1993, 1, 21) was added dropwise, and the mixture was incubated and stirred for 40 min. The completion of the reaction was monitored by TLC, and the reaction was quenched with 20% aqueous citric acid (200 mL), warmed to room temperature, and stirred for 3-4 h. EtOAc (200 mL) was added for separation, the organic phase was dried over sodium sulfate, filtered, concentrated, and the crude product was purified by column chromatography to obtain compound 6A as a colorless oil, 25.3 g, yield 77%.
[0101] Step 2:
[0102] Add compound 10 (20.0g, 1.0eq), MeOH (160mL), 10% Pd-C (1.0g) ammonium for...
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