3-Fluoro-6-nitro-o-xylene

Uses

Synthesis

443-82-3

1736-87-4

Example 16: Synthesis of 2-(2,3-dimethyl-4-nitrophenylamino)-2-methylpropan-1-ol 1. fuming nitric acid (1.4 g, 20.3 mmol) was cooled to 0 °C and slowly added to acetic anhydride (2.89 g, 28.4 mmol). 2. the above solution was added dropwise to a cooled (0 °C) solution of 3-fluoro-1,2-dimethylbenzene (1.0 g, 8.1 mmol) in acetic anhydride (4 ml) within 10 min. 3. The reaction mixture was stirred at 0 °C for 25 min and then slowly poured into ice water. 4. The aqueous phase was extracted with EtOAc (3×) and the organic phases were combined and washed sequentially with saturated aqueous solution of dilute NaHCO3 and brine. 5. The organic phase was dried over anhydrous Na2SO4, concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (mobile phase: hexane) to obtain 2,3-dimethyl-4-fluoro-1-nitrobenzene 0.74 g (54% yield) as a yellow oil, which was crystallized after standing. 6. The above nitro compound (0.576 g, 3.4 mmol) was mixed with 2-amino-2-methylpropanol (0.61 g, 6.8 mmol) in a reaction tube, sealed and immersed in an oil bath at 160 °C for 5 days. 7. TLC monitoring (unfolding agent: hexane) showed raw material remaining. The reaction mixture was cooled and diluted with EtOAc. 8. Purification by fast silica gel column chromatography (dry on sample; eluent: hexane/EtOAc=6:4) recovered the feedstock 2,3-dimethyl-4-fluoro-1-nitrobenzene 0.34 g (59% recovery) and afforded the target product 2-(2,3-dimethyl-4-nitrophenylamino)-2-methylpropan-1-ol 0.20 g (61% yield based on recovered feedstock).

References