4-ethoxy-3-iodoaniline

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 2-cyano-N-(2,4-dichloro-5-methoxyphenyl)acetamide (5.44 g, 21.0 mmol) in 350 mL of iso-propanol, under N2, was added (4-ethoxy-3-iodophenyl)amine (5.0 g, 19.30 mmol). This mixture was heated to reflux and triethylorthoformate (8.53 mL, 51.30 mmol) was added dropwise and the reaction mixture was heated at reflux overnight. The mixture was allowed to cool to room temperature and the yellow solid was collected by filtration, washed with iso-propanol, and dried overnight at ˜40° C. under reduced pressure to give 5.46 g (54%) of 2-cyano-N-(2,4-dichloro-5-methoxyphenyl)-3-[(4-ethoxy-3-iodophenyl)amino]prop-2-enamide as a yellow solid, mp >245° C.; MS (EI) m/z 531.01 (M)+ This mixture was heated to reflux the reaction mixture was heated at reflux overnight the yellow solid was collected by filtration washed with iso-propanol dried overnight at ˜40° C. under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of iron (3.81 g, 70 mmol) and ammonium chloride (5.47 g, 102 mmol) in 80 mL of ethanol and 25 mL of water was heated to reflux. 1-Ethoxy-2-iodo-4-nitrobenzene (5.0 g, 20 mmol) was added in portions and the reaction was heated at reflux for 1 hour. The hot mixture was filtered through Celite, washed with hot ethanol. The filtrate was concentrated in vacuo and treated with ethyl acetate and water. The organic layer was extracted, washed with brine, dried over magnesium sulfate and filtered. Removal of the solvent in vacuo provided 5.1 g of (4-ethoxy-3-iodophenyl)amine as a light brown oil; 1H NMR (400 MHz, DMSO-d6) δ 1.30 (s, 3H), 3.89 (q, 2H), 4.82 (bs, 2H), 6.53 (dd, 1H), 6.72 (d, 1H), 7.11 (d, 1H); MS (ES) m/z263.9 (M+H)+ was heated to reflux the reaction was heated at reflux for 1 hour The hot mixture was filtered through Celite washed with hot ethanol The filtrate was concentrated in vacuo treated with ethyl acetate and water The organic layer was extracted washed with brine dried over magnesium sulfate filtered Removal of the solvent in vacuo