4-Chloro-2-methoxybenzenamine

Dark Brown Low Melting Solid

A suspension of ferrum (5.0 equiv.), ammonium chloride (0.65 equiv.), and distilled water were refluxed for fifteen minutes. The nitro compound (1.0 equiv.) was added and the resulting reaction mixture was allowed to stir at reflux. When TLC showed that the reaction had stopped the mixture was neutralized by drop wise addition of a 5percent aqueous solution of sodium bicarbonate and it was filtered through Celite. The filtrate was washed thrice with ethyl acetate. The combined organic layers were washed once with brine and once with a 5percent aqueous solution of hydrochloric acid. The combined water layers were neutralized with 20percent aqueous sodium hydroxide and extracted thrice with ethyl acetate. The organic layers were combined, dried over anhydrous sodium sulfate and the solvent removed in vacuo. The pure product was obtained using column chromatography in ethyl acetate and hexanes but sometimes the product was kept crude. The purity of the product was determined using A. A suspension of 5-chloro-2-nitroanisole (7s) (2.67 g, 14.2 mmol) and 5percent Pt/C (200 nig) in methanol (60 niL) was placed under a hydrogen gas atmosphere and stirred 3 days. The suspension was filtered through diatoniaceous earth and concentrated. Purification by column chromatography (40 g), eluting with 15 to 30percent EA/hexanes, gave compound 7b (1.69 g, 76percent). 1H NMR (CHLOROFORM-d) δ: 6.70 - 6.83 (m, 2H), 6.58 - 6.64 (m, 1H), 3.84 (s, 3H), 3.76 (br. s., 2H). ESI-MS (m/z): Calcd. for C7H8ClNO: 158.0 (M+1); found: 158.0.5-Chlor-2-nitroanisol in THF are hydrogenated in the presence of H2 and Raney nickel at room temperature overnight. The catalyst is separated by filtration and the filtrate evaporated to dryness. The residue is purified by chromatography (35 g silica gel, eluent : DICHLOROMETHANE : methanol = 99 : 1). Yield : 69.5 percent, brown oilA mixture of 4-chloro-2-methoxy-l -nitrobenzene (938 mg, 5.0 mmol), tin(II) chloride dihydrate (3.38 g, 15 mmol) and EtOH (25 mL) was heated at reflux for 18 h. After cooling to rt, NaOH (aq, 4M, 50 mL) was added. The mixture was extracted with EtPreparation 91; 4-Chloro-2-methoxy-phenvlamine; To a suspension of 5-chloro-2-nitroanisole (10g, 53mmol) and potassium bicarbonate (28g, 280mol) in methanol (150mL) and water (150mL) was added sodium dithionite (28g, 159 mmol). The mixture was allowed to stir at room temperature for 2 hours. The reaction mixture was acidified to pH1 with concentrated hydrochloric acid and the resulting brown suspension was heated for 2 hours at 60°C before the solvent was evaporated under reduced pressure. The residual aqueous solution was washed with ethyl acetate, basified with sodium hydroxide pellets and re-extracted with ethyl acetate. The combined organic phase was washed with brine, dried over sodium sulfate and concentrated in vacuo to give the title compound in 64percent yield (5.35g). 'H NMR (DMSO-D6, 400MHz) zu : 3.66 (s, 3H), 4.76 (bs, 2H), 6.52 (m, 1H), 6.65 (m, 1 H), 6.79 (m, 1 H)Preparation 37; (4-Chloro-2-methoxyphenyl)amine; Sodium dithionite (28g, 159mmol) was added portionwise to a mixture of 5-chloro-2-nitroanisole (1Og, 53mmol) and potassium hydrogen carbonate (28g, 275.6mmol) in methanol (15OmL) and water (15OmL) and the reaction mixture was stirred at room temperature for 2 hours. The mixture was then acidified with concentrated hydrochloric acid and the mixture was heated at 6OGeneral procedure: A round-bottomed flask (25 mL) was charged with substrate (2 mmol), CuCl

4-Chloro-2-methoxyaniline is an important intermediate used for the synthesis of CXCR2 antagonists and some CD4-gp120 binding inhibitors.

Molecular Weight:157.60
XLogP3:1.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:157.0294416
Monoisotopic Mass:157.0294416
Topological Polar Surface Area:35.2
Heavy Atom Count:10
Complexity:110
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes