2-Bromo-4-ethylaniline

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 4-ethylaniline (1.76 g, 14.52 mmol) and NBS (2.58 g, 14.52 mmol) was added DMF (67 mL) and the reaction mixture was stirred at 0° C. for 10 min. The reaction mixture was purified by silica gel chromatography (0-50% ethyl acetate/hexanes) to provide 2-bromo-4-ethylaniline (2.7 g, 93% yield). LC/MS m/z 201.0 [M+H]+. The reaction mixture was purified by silica gel chromatography (0-50% ethyl acetate/hexanes)

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-bromo-4-ethylaniline (29.2 g) and cuprous cyanide (14.4 g) in dry pyridine (25.4 g) was stirred for 16 hours at 160° C. After cooling to 60° C., the resultant mixture was poured into a mixture (250 ml) of conc. aqueous ammonia and water (1:1) with stirring. To the resultant mixture was added ethyl acetate (300 ml) with stirring. Insoluble materials were filtered off. The organic layer was washed three times with water and with aqueous solution saturated with sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give an oily residue, to which was added benzene and concentrated under reduced pressure. These operations were repeated twice to remove pyridine. The resultant oily residue was subjected to a column chromatography using silica gel (developing solvent: a mixture of benzene and hexane (3:1)) to give 2-amino-4-ethylbenzonitrile (16.4 g). After cooling to 60° C. with stirring with stirring Insoluble materials were filtered off The organic layer was washed three times with water with aqueous solution saturated with sodium chloride, dried over anhydrous magnesium sulfate concentrated under reduced pressure to give an oily residue concentrated under reduced pressure to remove pyridine a mixture of benzene and hexane (3:1))

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

Procedure: 4-Ethylphenylamine (1.00 g, 7.52 mmol, 1 equiv) was dissolved in chloroform (40 mL) and placed into an ice bath. NBS (1.34 g, 1 equiv) was then added into the solution in small portions. The mixture was warmed to room temperature and stirred for 2 hours. EtOAc (˜200 mL) was added and the mixture was filtered. The filtrate was washed with saturated aqueous K2CO3 (200 mL), saturated aqueous NaHCO3 (200 mL), and brine (200 mL), dried over magnesium sulfate and concentrated. The residue was purified by silica gel flash column chromatography using 5% to 20% EtOAc in hexanes to afford the title compound as light brown oil (1 g). MS (ES) m/z 200.0 (M+H+). placed into an ice bath the mixture was filtered The filtrate was washed with saturated aqueous K2CO3 (200 mL), saturated aqueous NaHCO3 (200 mL), and brine (200 mL) dried over magnesium sulfate concentrated The residue was purified by silica gel flash column chromatography

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 4-ethylaniline (1.76 g, 14.52 mmol) and NBS (2.58 g, 14.52 mmol) was added DMF (67 mL) and the reaction mixture was stirred at 0° C. for 10 min. The reaction mixture was purified by silica gel chromatography (0-50% ethyl acetate/hexanes) to provide 2-bromo-4-ethylaniline (2.7 g, 93% yield). LC/MS m/z 201.0 [M+H]+. The reaction mixture was purified by silica gel chromatography (0-50% ethyl acetate/hexanes)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 4-ethylaniline (1.76 g, 14.52 mmol) and NBS (2.58 g, 14.52 mmol) was added DMF (67 mL) and the reaction mixture was stirred at 0° C. for 10 min. The reaction mixture was purified by silica gel chromatography (0-50% ethyl acetate/hexanes) to provide 2-bromo-4-ethylaniline (2.7 g, 93% yield). LC/MS m/z 201.0 [M+H]+. The reaction mixture was purified by silica gel chromatography (0-50% ethyl acetate/hexanes)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 4-ethylaniline (1.76 g, 14.52 mmol) and NBS (2.58 g, 14.52 mmol) was added DMF (67 mL) and the reaction mixture was stirred at 0° C. for 10 min. The reaction mixture was purified by silica gel chromatography (0-50% ethyl acetate/hexanes) to provide 2-bromo-4-ethylaniline (2.7 g, 93% yield). LC/MS m/z 201.0 [M+H]+. The reaction mixture was purified by silica gel chromatography (0-50% ethyl acetate/hexanes)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 4-ethylaniline (1.76 g, 14.52 mmol) and NBS (2.58 g, 14.52 mmol) was added DMF (67 mL) and the reaction mixture was stirred at 0° C. for 10 min. The reaction mixture was purified by silica gel chromatography (0-50% ethyl acetate/hexanes) to provide 2-bromo-4-ethylaniline (2.7 g, 93% yield). LC/MS m/z 201.0 [M+H]+. The reaction mixture was purified by silica gel chromatography (0-50% ethyl acetate/hexanes)

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-bromo-4-ethylaniline (29.2 g) and cuprous cyanide (14.4 g) in dry pyridine (25.4 g) was stirred for 16 hours at 160° C. After cooling to 60° C., the resultant mixture was poured into a mixture (250 ml) of conc. aqueous ammonia and water (1:1) with stirring. To the resultant mixture was added ethyl acetate (300 ml) with stirring. Insoluble materials were filtered off. The organic layer was washed three times with water and with aqueous solution saturated with sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give an oily residue, to which was added benzene and concentrated under reduced pressure. These operations were repeated twice to remove pyridine. The resultant oily residue was subjected to a column chromatography using silica gel (developing solvent: a mixture of benzene and hexane (3:1)) to give 2-amino-4-ethylbenzonitrile (16.4 g). After cooling to 60° C. with stirring with stirring Insoluble materials were filtered off The organic layer was washed three times with water with aqueous solution saturated with sodium chloride, dried over anhydrous magnesium sulfate concentrated under reduced pressure to give an oily residue concentrated under reduced pressure to remove pyridine a mixture of benzene and hexane (3:1))

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-bromo-4-ethylaniline (29.2 g) and cuprous cyanide (14.4 g) in dry pyridine (25.4 g) was stirred for 16 hours at 160° C. After cooling to 60° C., the resultant mixture was poured into a mixture (250 ml) of conc. aqueous ammonia and water (1:1) with stirring. To the resultant mixture was added ethyl acetate (300 ml) with stirring. Insoluble materials were filtered off. The organic layer was washed three times with water and with aqueous solution saturated with sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give an oily residue, to which was added benzene and concentrated under reduced pressure. These operations were repeated twice to remove pyridine. The resultant oily residue was subjected to a column chromatography using silica gel (developing solvent: a mixture of benzene and hexane (3:1)) to give 2-amino-4-ethylbenzonitrile (16.4 g). After cooling to 60° C. with stirring with stirring Insoluble materials were filtered off The organic layer was washed three times with water with aqueous solution saturated with sodium chloride, dried over anhydrous magnesium sulfate concentrated under reduced pressure to give an oily residue concentrated under reduced pressure to remove pyridine a mixture of benzene and hexane (3:1))

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-bromo-4-ethylaniline (29.2 g) and cuprous cyanide (14.4 g) in dry pyridine (25.4 g) was stirred for 16 hours at 160° C. After cooling to 60° C., the resultant mixture was poured into a mixture (250 ml) of conc. aqueous ammonia and water (1:1) with stirring. To the resultant mixture was added ethyl acetate (300 ml) with stirring. Insoluble materials were filtered off. The organic layer was washed three times with water and with aqueous solution saturated with sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give an oily residue, to which was added benzene and concentrated under reduced pressure. These operations were repeated twice to remove pyridine. The resultant oily residue was subjected to a column chromatography using silica gel (developing solvent: a mixture of benzene and hexane (3:1)) to give 2-amino-4-ethylbenzonitrile (16.4 g). After cooling to 60° C. with stirring with stirring Insoluble materials were filtered off The organic layer was washed three times with water with aqueous solution saturated with sodium chloride, dried over anhydrous magnesium sulfate concentrated under reduced pressure to give an oily residue concentrated under reduced pressure to remove pyridine a mixture of benzene and hexane (3:1))

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-bromo-4-ethylaniline (29.2 g) and cuprous cyanide (14.4 g) in dry pyridine (25.4 g) was stirred for 16 hours at 160° C. After cooling to 60° C., the resultant mixture was poured into a mixture (250 ml) of conc. aqueous ammonia and water (1:1) with stirring. To the resultant mixture was added ethyl acetate (300 ml) with stirring. Insoluble materials were filtered off. The organic layer was washed three times with water and with aqueous solution saturated with sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give an oily residue, to which was added benzene and concentrated under reduced pressure. These operations were repeated twice to remove pyridine. The resultant oily residue was subjected to a column chromatography using silica gel (developing solvent: a mixture of benzene and hexane (3:1)) to give 2-amino-4-ethylbenzonitrile (16.4 g). After cooling to 60° C. with stirring with stirring Insoluble materials were filtered off The organic layer was washed three times with water with aqueous solution saturated with sodium chloride, dried over anhydrous magnesium sulfate concentrated under reduced pressure to give an oily residue concentrated under reduced pressure to remove pyridine a mixture of benzene and hexane (3:1))

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

Procedure: 2-bromo-4-ethylaniline and glycerol can be combined to form 6-ethyl-8-bromoquinoline,