4-Nitrobenzyl hydrogen malonate is a reagent used in the synthesis of (±)-thienamycin, a β-Lactam antibiotics. Also, it is useful for chiral key intermediate of carbapenem syntheses.
Preparation of mono-4-nitrobenzyl malonate:
In a flame-dried 150 mL pressure tube under argon, add 5.00 g (34.7 mmol) of Meldrum's acid and 40 mL of anhydrous MeCN.
Add 5.58 g (36.4 mmol) of p-nitrobenzyl alcohol to the resulting solution.
Cap the tube tightly and reflux the reaction overnight.
Concentrate the reaction mixture under reduced pressure.
Purify the residue using column chromatography with a 55/45 hexane/EtOAc mixture.
The resulting product is mono-4-nitrobenzyl malonate with a yield of 87%.
Meldrum acid (5.00 g, 34.7 mmol) and anhydrous acetonitrile (40 mL) were added to a flame-dried 150 mL pressure tube under argon protection. To this solution was added p-nitrobenzyl alcohol (5.58 g, 36.4 mmol), the pressure tube was sealed and the reaction was carried out overnight under reflux conditions. Upon completion of the reaction, the solvent was removed by concentration under reduced pressure and the crude product was purified using column chromatography (eluent ratio 55:45 hexane/ethyl acetate) to afford mono-p-nitrobenzyl malonate (16a, 6.86 g, 27.1 mmol) as an off-white solid in 83% yield. A small amount of the product (1.00 g) was recrystallized by tert-butanol/hexane mixed solvent to give purified mono-p-nitrobenzyl malonate (16a, 225 mg, 0.889 mmol) as a white solid.
[1] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 21, p. 4933 - 4936
[2] Tetrahedron, 2001, vol. 57, # 9, p. 1837 - 1847
[3] Tetrahedron Letters, 2003, vol. 44, # 40, p. 7499 - 7502
