Description
Methyl 3-formyl-2-nitrobenzoate is a phase transfer catalyst used to synthesize chlorinated hydrocarbons from inorganic chloride. It is soluble in organic solvents and can synthesize hydrochloric acid, sodium chloride, and zinc chloride. Methyl 3-formyl-2-nitrobenzoate is also used as a catalyst for producing polychlorinated biphenyls. It is hydrolyzed by water to release methyl 3-hydroxy-2-nitrobenzoate.
Uses
Methyl 3-Formyl-2-nitrobenzoate is a reagent used in the synthesis of PARP inhibitors. Intermediate of Niraparib (N481400), a novel oral poly(ADP-ribose)polymerase (PARP) inhibitor efficacious in BRCA-1 and -2 mutant tumors.
Synthesis
Step C: Synthesis of methyl 3-formyl-2-nitrobenzoate; N-methylmorpholine oxide (NMO, 6.10 g, 52.07 mmol) was added to a solution of acetonitrile (150 mL) containing methyl 3-(bromomethyl)-2-nitrobenzoate (7.13 g, 26.023 mmol) and 4A molecular sieves (35.32 g) under nitrogen protection. The reaction mixture was stirred at room temperature for 1.5 hours. Subsequently, the reaction mixture was diluted with ethyl acetate (600 mL) and the insoluble material was removed by vacuum filtration. The filtrate was washed sequentially with water (100 mL), 1N HCl (100 mL) and brine (150 mL) and then dried with anhydrous sodium sulfate. The solvent was removed by concentration under reduced pressure and the residue was purified by fast column chromatography on silica gel, using ethyl acetate/hexane (1:3) as eluent to afford methyl 3-formyl-2-nitrobenzoate as an off-white solid (4.04 g, 74% yield). The structure of the product was confirmed by 1H NMR (CDCl3): δ 3.95 (s, 3H), 7.77 (t, 1H), 8.18 (dd, 1H), 8.28 (dd, 1H), 9.98 (s, 1H).
References
[1] Patent: WO2005/66136, 2005, A1. Location in patent: Page/Page column 88-89
[2] Patent: WO2009/87381, 2009, A1. Location in patent: Page/Page column 35-36
[3] Journal of Medicinal Chemistry, 2009, vol. 52, # 22, p. 7170 - 7185
[4] Organic Process Research and Development, 2011, vol. 15, # 4, p. 831 - 840
[5] Patent: WO2007/113596, 2007, A1. Location in patent: Page/Page column 77
