1-Bromo-2-fluoro-3,5-dinitrobenzene → 2-Bromo-1-fluoro-4-nitrobenzene

To a solution of 1-bromo-2-fluoro-3,5-dinitrobenzene (5.4 g, 20.38 mmol, 1 equiv) in acetic acid (200 mL) at room temperature (using a water bath) was added powdered iron portion-wise (5.70 g, 102 mmol, 5 equiv). The resulting solution was stirred for 3 hours keeping the temperature of the mixture below 30° C. LCMS indicated the formation of three products: 3-bromo-2-fluoro-5-nitrobenzenamine-F3 (86%), 3-bromo-4-fluoro-5-nitrobenzenamine-F2 (5%), and 5-bromo-4-fluorobenzene-1,3-diamine-F1 (9%). [Note: After completion of this experiment, to identify regioisomers, 3-bromo-2-fluoro-5-nitrobenzenamine was diazotized and deaminated (see, E. S. Adams and K. L. Rinehart. The Journal of Antibiotics 1994, 47 (12), 1456-1465) to give 3-bromo-4-fluoro-nitrobenzene. This was compared to an authentic sample obtained from a commercial source]. DCM was added to the mixture, and the resulting mixture was filtered through a pad of Celite, and the pad of Celite was rinsed with MeOH. The filtrate was evaporated to dryness. The residue was quenched with 2M NH3/MeOH followed by concentrating to dryness and repeating once—silica gel was added at this stage so that the crude product was absorbed directly on to silica gel. The crude product was purified by column chromatography on silica gel using DCM to give the desired product 3-bromo-2-fluoro-5-nitrobenzenamine (F1 on TLC; 1.87 g, 39%) as a yellow solid.

1. customthe temperature of the mixture below 30° C

ORD record

ord-e0e9ce077c5044e093ae67b12468fc7d

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08710223B2