392-09-6

Methyl 2-fluoro-4-nitrobenzoate is a pharmaceutical intermediate compound used in the preparation of the anticancer drug Venetoclax.  Venetoclax is a B-cell lymphoma-2 (BCL-2) inhibitor used in the treatment of adults with chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL), or newly diagnosed chronic lymphocytic lymphoma (SLL).

Step 1: Concentrated sulfuric acid (2.9 ml) was slowly added to a methanolic solution of 2-fluoro-4-nitrobenzoic acid (1 g, 5.402 mmol). The reaction mixture was heated to reflux overnight and subsequently cooled to room temperature and concentrated under reduced pressure. The residue was diluted with ethyl acetate and washed with saturated sodium bicarbonate solution. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to afford pure methyl 2-fluoro-4-nitrobenzoate (1.05 g, 98% yield).

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[4] Patent: WO2004/37814, 2004, A1. Location in patent: Page 166-167
[5] Patent: EP1810969, 2007, A1. Location in patent: Page/Page column 41