3-Bromo-5-fluoro-2-methylbenzenamine

Ammonium chloride (571 mg, 10.7 mmol) was added to 1-bromo-5-fluoro-2- methyl-3-nitrobenzene (500 mg, 2.14 mmol) and iron (powder) (0.6 g, 10.68 mmol) in water (24 mL) and ethanol (24 mL). The reaction was refluxed for 5 hours then filtered through celite and the filter cake washed with ethanol (100 mL) and EtOAc (100 mL). The organics were removed in vacuo to leave an aqueous solution which was extracted with DCM (3 x 30 mL). The organics were isolated and concentrated to give crude 3-bromo-5-fluoro-2-methyl-aniline (390 mg, 1 .87 mmol, 87.7percent) which was clean by NMR and used without further purification.[00403] 1H NMR (DMSO-d6): O 6.60 (dd, J= 2.8 and 8.4 Hz, 1H), 6.42 (dd, J = 2.8 and11.6 Hz, 1 H), 5.54 (bs, 2H), 2.09 (5, 3H).A mixture of above prepared compound (15.0 g, 64.4 mmol), Fe (18.0 g, 0.32 mol), con. HCl (2 mL) in MeOH (150 mL) and water (30 mL) was stirred at reflux for 4 h. Then the mixture was adjusted to pH 12 with aqueous NaOH solution and filtered. The solvent was removed and diluted with water. Extracted with ethyl acetate, dried, concentrated. The residue was purified by column chromatograph (ethyl acetate in petroleum ether, 7percent) to get compound 0104-69 (5.8 g, 44percent) as yellow oil. LCMS: 204 [M+l]Step 23a: 3-Bromo-5-fluoro-2-methylbenzenamine (Compound 0104-69)[0280]To a solution of 4-fluoro-2-nitrotoluene (10.0 g, 64.4 mmol) in trifluoroacetic acid (40 mL) was added con. sulfuric acid (12.5 mL) followed by NBS (17.2 g, 96.6 mmol) and the reaction mixture was stirred at room temperature for 16 h. Then the reaction mixture was poured into ice and water and stirred for 15 min. Extracted with ethyl acetate and the organic layer was washed with brine, dried, concentrated to get compound 1-bromo-5-fluoro-2-methyl-3-nitrobenzene (15.0 g, 100percent) as a yellow oil. Solution of trifluoroacetic acid (40 mL) of 4-fluoro-2-nitrotoluene (10.0g, 64.4mmol)To, after addition of concentrated sulfuric acid (12.5 mL), was added NBS (17.2g, 96.6mmol), the reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was then poured into ice water, and the mixture was stirred for 15 minutes. And extracted with ethyl acetate, the organic layer was washed with brine, dried and concentrated to give compound 1-bromo-5-fluoro-2-methyl-3- nitrobenzene (15.0g, 100percent) as a yellow oil . MeOH (150mL) and the compound medium prepared in the above water (30mL) (15.0g, 64.4mmol), Fe (18.0g, 0.32mol), were stirred for 4 hours under reflux the mixture of concentrated HCl (2mL). Then the mixture with aqueous NaOH to pH12 adjusted and filtered. The solvent was removed and diluted with water. And extracted with ethyl acetate, dried, and concentrated. The residue was purified by column chromatography (chromatograph) (petroleum ether containing ethyl acetate, 7percent), compound 0104-69 (5.8g, 44percent) as a yellow oil.

Molecular Weight:204.04
XLogP3:2.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:202.97459
Monoisotopic Mass:202.97459
Topological Polar Surface Area:26
Heavy Atom Count:10
Complexity:120
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes