Methyl α-Diazo-β-Oxo-1-Pyrrolidinepropanoate

[135747-07-8] C8H11N3O3 (MW 197.1912) InChI = 1S/C8H11N3O3/c1-14-8(13)6(10-9)7(12)11-4-2-3-5-11/h2-5H2,1H3 InChIKey = PBPMNSGKBHRNKM-UHFFFAOYSA-N (reagent used as precursor to metal carbenes, intramolecular CH insertion reactions,1, 2 and cyclopropanation of alkenes2, 3) Physical Data: pale yellow crystalline solid, Rf 0.60 (Et2O); 1H NMR (300 MHz, CDCl3) δ 3.95 (s, 3H), 3.50 (m, 4H), 2.10 (m, 4H); IR (film) 2960, 2870, 2110, 1710, 1620 cm−1.1 Solubility: sol in most organic solvents. Form Supplied in: not commercially available. Preparative Method: 1-3 potassium hydroxide (5.6 g, 100 mmol, 1.0 equiv) was dissolved in methanol (200 mL) and the solution was cooled to 0 °C. Dimethyl malonate (11.4 mL, 100 mmol, 1.0 equiv) was added to this solution and the reaction mixture was stirred at 0 °C for 1 h. The reaction mixture was then allowed to warm up to rt, and stirring was continued for an additional 1 h. The white crystals of the salt were isolated by vacuum filtration and dried under vacuum for 3 h. The potassium carboxylate salt (3.9 g, 25 mmol, 1.00 equiv) was suspended in DCM (50 mL) at 0 °C under a positive pressure of Ar. Oxalyl chloride (2.53 mL, 30 mmol, 1.20 equiv) was next added dropwise over 5 min followed by the addition of DMF (5–10 drops). The resulting solution was stirred for 1 h at 0 °C and then at rt for 1 h. Solvent was removed under reduced pressure and the solid was dissolved in 50 mL of DCM, which was also removed under reduced pressure. The solid was dissolved in 50 mL of DCM and pyrrolidine (4.1 mL, 50 mmol, 2.00 equiv) was added dropwise at 0 °C. The reddish mixture was stirred for 1 h at 0 °C, then at rt for 1 h, and treated with 10% HCl (50 mL). The organic phase was separated, dried over MgSO4, filtered through Celite™, and concentrated under vacuum to afford quantitatively the corresponding β-amido ester. The crude product was then dissolved in acetonitrile (50 mL) and treated with triethylamine (4.15 mL, 30 mmol, 1.20 equiv) and tosyl azide4 (5.92 g, 30 mmol, 1.20 equiv). The mixture was stirred at rt for 16 h. Following evaporation of the solvent, the crude product was suspended in diethyl ether and filtered. The resulting organic phase was washed twice with 3 N NaOH and once with brine, then dried over anhydrous MgSO4, filtered through Celite™, and concentrated under vacuum. The yellow residue was purified by flash chromatography on silica gel using hexane/ethyl acetate (3:1) as eluent. The product was isolated as a yellow liquid that solidified upon standing in the fridge (0 °C). Yield: 95% (4.68 g). Purification: the title compound can be readily purified by flash chromatography on silica gel with a diethyl ether/hexane solvent system to obtain a yellow oil that solidifies upon standing in the fridge (0 °C). Handling, Storage, and Precautions: although no one has experienced any problem in the handling of the title compound, care should be taken when manipulating it due to the explosive nature of diazo compounds. The title compound is stable for more than 6 months when stored at 0 °C. The toxicity is unknown.

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