4-Chloro-3-methoxyaniline

General procedure: To a flame-dried 25 mL round bottom flask was charged activated Mg (7.5 mmol, 1.5 eq.) and 5 mL anhydrous THF. To this suspension was added 2 drops of 1, 2-dibromoethane. After 5 min, a solution of Aryl bromide (5 mmol, 1.0 eq.) in 5 mL anhydrous THF was slowly added to the suspension of Mg at room temperature. The reaction was mildly exothermic. The Grignard reagent was titrated and 1 mmol of this reagent was added to a flame-dried reaction vial. The solution was diluted with 3 mL anhydrous toluene and after cooling to the target temperature T, a solution of oxaziridine (1.2 mmol, 1.2 eq.) in 1 mL anhydrous toluene was added. The reaction was maintained at the targeted temperature T for time t before being quenched with saturated aqueous NHIron based nanomaterial (12 mg, 3.6percent) was placed into an oven dried 5 mL microwave reaction vial containing a PTFE-coated magnetic stir bar. The reaction vial was covered with a rubber septum and 0.5 mL aqueous solution of 2 wt.percent TPGS-750-M was added via syringe. The mixture was stirred at ft for 1 mm. The septum was opened and NaBH4 (57 mg, 1.5 mmol) was slowly added to the mixture. During addition NaB H4, reaction mixture was turned black with evolution of hydrogen gas. 1-Chloro-2-methoxy-4- nitrobenzene (187 mg, 1 mmol) was then added and the vial was filled argon and again covered. The contents were stirred vigorously until complete consumption of the starting material (about 4 h). The resulting mixture was extracted with EtOAc (0.4 mL x 2). The organic layer was then separated (with the aid of centrifuge, if needed) and dried over anhydrous Na2504, and the volatiles were removed under reduced pressure and purified by flash chromatography over silica gel with EtOAc/hexanes to obtain 4-chloro-3- methoxyaniline 54 (151 mg, 0.96 mmol, 96percent). Brown solid, mp 79-80 °C; ‘H NMR (400 MHz, DMSO) 6.98 (d, J= 8.4, 1H), 6.34 (d, J= 1.8, 1H), 6.16 (dd, J= 8.4, 1.9, 1H), 5.23 (s, 2H), 3.74 (s, 3H). GC-MS, mlz: 157 [Mj.First, NaBH4 (1 mmol) was used as a reducing agent forthe conversion of Ag (+ 1) to Ag (0) in methanol at roomtemperature for 2 h. After that, the Ag/MMT was filtered andused as a catalyst. Then, in a typical procedure, a mixtureof 4-nitrophenol (0.1 mmol), KOH (0.15 mmol), isopropylalcohol (3 mL), and Ag/MMT catalyst (50 mg) 1.01 wtpercentwas stirred at room temperature for an appropriate time(Scheme 2). After the completion of the reaction (monitoredby GC), the catalyst was separated by filtration. The ensuingproduct was extracted with ethyl acetate and repeatedlywashed with water (3–4 times) to remove KOH. The resultingsolvent was evaporated to dryness in vacuum.4-Chloro-3-methoxy-phenylamine Ammonium chloride (14.3 g, 267 mmol) and iron powder (325 mesh, 14.9 g, 267 mmol) were dissolved in water (100 ml_). A solution of 2-chloro-5-nitroanisole (10 g, 53.3 mmol) in tetrahydrofuran (50 ml_) and methanol (50 ml_) was added. The mixture was stirred at 804-Chloro-3-methoxy-phenylamineAmmonium chloride (14.3 g, 267 mmol) and iron powder (325 mesh, 14.9 g, 267 mmol) were dissolved in water (100 ml_). A solution of 2-chloro-5-nitroanisole (10 g, 53.3 mmol) in tetrahydrofuran (50 ml_) and methanol (50 ml_) was added. The mixture was stirred at 80 5-NITRO-2-CHLORO aniline (50.0 g, 0.289 mol) in 30 percent sulfuric acid (300 ml) was stirred at RT FOR 2 h. Sodium nitrite (21.0 g, 0.304 mol) in water (50 ml) was added slowly at 0°C and maintained at this temperature for 15 min. This diazotized solution was added slowly to dilute sulfuric acid (50 percent, 250 ML) at 110 °C. Stirring was continued for 15 min. After cooling to RT, ice water was added, the mixture extracted with ethylacetate, washed with water, brine and dried over NA2SO4. The product obtained upon concentration was purified by column chromatography. Yield 12.0 g, 24. 0 percent. [00162] To K2CO3 (23.84 g, 0.172 mol) and 2-chloro-5-nitrophenol (10.0 g, 0.0576 mol) in ACETONITRILE (100 ml) was added methyl iodide (19.60 g, 0.138 mol) at 0°C. The reaction mixture was warmed to RT and stirred overnight. Water was added and extracted with ethyl acetate. The organic layer was washed with water, brine and dried over NA2SO4. The product obtained upon concentration was purified by column chromatography. Yield : 6.0 g, 55. 55 percent. [00163] 2-CHLORO-5-NITRO ANISOLE (6.0 g, 0.032 mol) in MEOH (45 ml) was added slowly to stannous chloride (15.1 g, 0.08 mol) in conc. HCI (110 ml) at 40 °C and the temperature was slowly raised to 50 ° C. Stirring was continued for 2h, the reaction cooled to RT, basified with 50 percent NAOH solution and extracted by ethyl acetate. The organic layer was washed with water, brine and dried over NA2SO4. The product obtained upon concentration was purified by column chromatography. Yield : 4.0 g, 79.36 percent. [00164] To triethylamine (3.83 g, 0.037 mol) and 3-methoxy-4- chloro aniline (3.0 g, 0.0190 mol) in benzene (50 ML) was added trimethylacetylchloride (2.75 g, 0.022 mol) slowly at 0 °C. The temperature was raised to RT and stirred overnight. The reaction mixture was added to ice and extracted with ethyl acetate. The organic layer was washed with water, brine, dried over NA2SO4 and concentrated. Yield : 3.7 g, 80.43 percent. [00165] To N-PIVALOYL-3-METHOXY-4-CHLOROANILINE (1.50 g, 0.0062 mol) in THF (30 ML) was added n-butyl lithium (1.0 g, 0.0156 mol) at 0 °C and the reaction stirred for 2 hr. After cooling to-70 °C, methyl isonicotinate (1.3 g, 0.0094 mol) in THF (12 ml) was added slowly. The reaction was warmed to rt and stirred overnight and then quenched with water and extracted with ether. The water layer was further extracted and the combined ether layers were washed with water, brine and dried over NA2SO4. The product obtained upon concentration was purified by column chromatography. Yield 0.50 g, 23. 25 percent. [00166] The protected ketone from step 5 (0.500g, 0. 0014MOL) was suspended in concentrated HCI (5 ml) at RT, then the temperature was raised to 95 °C and the mixture stirred over night. The mixture was cooled to RT, basified with 20 percent NAOH solution and extracted with DCM. The combined organic layer was washed with water, brine and dried over NA2SO4. The product obtained upon concentration was purified by column chromatography using basic alumina to yield title compound (0.140 g, 37.33percent).5-Nitro-2-chloro aniline (50.0 g, 0.289 mol) in 30 percent sulfuric acid (300 ml) was stirred at RT for 2 h. Sodium nitrite (21.0 g, 0.304 mol) in water (50 ml) was added slowly at 0°C. After 15 mins, this solution was added slowly to dilute sulfuric acid (50 percent, 250 ml) at 110 °C. Stirring was continued for 15 min. The reaction mixture was cooled to RT, ice water was added, extracted with ethylacetate, washed with water, brine and dried over NA2SO4. The phenol product obtained upon concentration was purified by column chromatography. Yield 12.0 g, 24.0 percent. [00153] K2CO3 (23.84 g, 0.172 mol) was added to 2-chloro-5- nitrophenol (10.0 g, 0.058 mol) in acetonitrile (100 ml) at RT. After cooling to 0 °C, methyl iodide (19.6 g, 0.138 mol) was added slowly and the reaction mixture stirred at RT overnight. Water (100 ml) was added and the aqueous layer extracted with ethyl acetate. The organic layer was washed with water, brine and dried over NA2SO4. The product obtained upon concentration was purified by column chromatography to yield the ANISOLE (6.0 g, 55.55percent). [00154] 2-CHLORO-5-NITRO ANISOLE (6.0 g, 0.032 mol) in MEOH (45 ml) was added slowly to stannous chloride (15.1 g, 0.08 mol) in conc. HCI (110 ml) at 40 °C and the temperature was slowly raised to 50 ° C. Stirring was continued for 2 h. After cooling to RT, the reaction mixture was basified with 50 percent NAOH solution, extracted by ethyl acetate, washed with water, then brine and dried over NA2SO4. 3-METHOXY-4-CHLOROANILINE was obtained upon concentration and was purified further by column chromatography. Yield : 4.0 g, 79.36 percent. [00155] To 3-METHOXY-4-CHLOROANILINE (2.0 g, 0.0126 mol) in trichloroethylene (30 ml) was added BC13 (2.18 g, 1 M solution in DCM, 0.0188 mol) AT 0 °C. After stirring for 10 min, 4-CYANOPYRIDINE (1.6 g, 0.0153 mol) and AIC13 (2.35 g, 0.018 mol) were added and the temperature was raised to RT, with further stirring for 30 min. The temperature was raised further to 85 °C and maintained at the same temperature for 1 h. DCM was distilled off and the solution was stirred at 115 °C for 4 h and then at RT over night. 3N HCI was added at RT and the reaction mixture REFLUXED for 1.5 h. The reaction mixture was allowed to cool and made basic using NAOH (6 N), diluted with water and extracted with DCM, washed with water, brine and dried over NA2SO4. The crude title compound was obtained upon concentration and was purified by column chromatography. Yield : 0.50 g, 15 percent.Pd(C) (10percent, 142mg, 0.13mmol, 0.1 eq. Pd) was added to a solution of 1-chloro-2-methoxy-4-nitrobenzene (250mg, 1.33mmol, 1.0 eq.) in 10ml of EtOAc. The vessel was evacuated, backfilled with H

Molecular Weight:157.60
XLogP3:2
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