N'-[2-(dimethylamino)ethyl]-N,N,N'-trimethylethane-1,2-diamine

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:

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:

Conditions: temp:-75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Butyl lithium (47.5 ml of 2.22M solution, 105.6 mmole) was added slowly to a solution of pentamethyldiethylenetriamine (15 ml) and 4-fluoroanisole (12.61 g, 0.1 mole) in THF (150 ml) at -70° C. The solution was stirred for 2 hr at -75° C. and a solution of pyridine-4-aldehyde (9.55 ml, 0.1 mole) in THF was added at -75° C. The mixture was allowed to warm to 25° C. slowly and then quenched with ammonium chloride solution. The mixture was diluted with ethyl acetate and the organic layer was separated. The organic layer was washed with water and 3N hydrochloric acid. The acid washes were then basified with sodium hydroxide and extracted with ether and the ether solution concentrated in vacuo. The crude product was recrystallized from 80% ethanol to give (2-fluoro-5-methoxy-phenyl)-4-pyridylmethanol as a white powder (12.22 g+3.12 g second crop, 65.8% total yield). to warm to 25° C. slowly quenched with ammonium chloride solution The mixture was diluted with ethyl acetate the organic layer was separated The organic layer was washed with water and 3N hydrochloric acid extracted with ether the ether solution concentrated in vacuo The crude product was recrystallized from 80% ethanol to give

Conditions: temp:-75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Butyl lithium (47.5 ml of 2.22M solution, 105.6 mmole) was added slowly to a solution of pentamethyldiethylenetriamine (15 ml) and 4-fluoroanisole (12.61 g, 0.1 mole) in THF (150 ml) at -70° C. The solution was stirred for 2 hr at -75° C. and a solution of pyridine-4-aldehyde (9.55 ml, 0.1 mole) in THF was added at -75° C. The mixture was allowed to warm to 25° C. slowly and then quenched with ammonium chloride solution. The mixture was diluted with ethyl acetate and the organic layer was separated. The organic layer was washed with water and 3N hydrochloric acid. The acid washes were then basified with sodium hydroxide and extracted with ether and the ether solution concentrated in vacuo. The crude product was recrystallized from 80% ethanol to give (2-fluoro-5-methoxy-phenyl)-4-pyridylmethanol as a white powder (12.22 g+3.12 g second crop, 65.8% total yield). to warm to 25° C. slowly quenched with ammonium chloride solution The mixture was diluted with ethyl acetate the organic layer was separated The organic layer was washed with water and 3N hydrochloric acid extracted with ether the ether solution concentrated in vacuo The crude product was recrystallized from 80% ethanol to give

Conditions: temp:-75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Butyl lithium (70 ml of 2.22M solution, 155 mmole) was added to a solution of pentamethyldiethylenetriamine (23.3 ml, 155 mmole) in THF (250 ml) at -70° C. The solution was stirred for 5 min and 1,4-difluorobenzene (17.7 g, 155 mmole) in THF was added at -70° C. The solution was stirred for 2 hr during which time it was cooled to -75° C. and 4-cyanopyridine (15.6 g, 150 mmole) in THF was added at -75° C. The mixture was allowed to warm to 25° C. slowly and then quenched with ammonium chloride solution. The mixture was diluted with ether and the organic layer was separated. The organic layer was washed with water and 3N hydrochloric acid. The acid washes were stirred for 2 hr and basified with sodium hydroxide. The basic mixture was extracted with ether and the ether solution concentrated in vacuo. The crude product was purified by chromatography on silica eluting with ethyl acetate-hexane (20:1) to give 4-(2,5-difluorobenzoyl)pyridine (16.9 g, 51.5%). The solution was stirred for 2 hr during which time it to warm to 25° C. slowly quenched with ammonium chloride solution The mixture was diluted with ether the organic layer was separated The organic layer was washed with water and 3N hydrochloric acid The acid washes were stirred for 2 hr and basified with sodium hydroxide The basic mixture was extracted with ether the ether solution concentrated in vacuo The crude product was purified by chromatography on silica eluting with ethyl acetate-hexane (20:1)

Conditions: temp:-75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Butyl lithium (70 ml of 2.22M solution, 155 mmole) was added to a solution of pentamethyldiethylenetriamine (23.3 ml, 155 mmole) in THF (250 ml) at -70° C. The solution was stirred for 5 min and 1,4-difluorobenzene (17.7 g, 155 mmole) in THF was added at -70° C. The solution was stirred for 2 hr during which time it was cooled to -75° C. and 4-cyanopyridine (15.6 g, 150 mmole) in THF was added at -75° C. The mixture was allowed to warm to 25° C. slowly and then quenched with ammonium chloride solution. The mixture was diluted with ether and the organic layer was separated. The organic layer was washed with water and 3N hydrochloric acid. The acid washes were stirred for 2 hr and basified with sodium hydroxide. The basic mixture was extracted with ether and the ether solution concentrated in vacuo. The crude product was purified by chromatography on silica eluting with ethyl acetate-hexane (20:1) to give 4-(2,5-difluorobenzoyl)pyridine (16.9 g, 51.5%). The solution was stirred for 2 hr during which time it to warm to 25° C. slowly quenched with ammonium chloride solution The mixture was diluted with ether the organic layer was separated The organic layer was washed with water and 3N hydrochloric acid The acid washes were stirred for 2 hr and basified with sodium hydroxide The basic mixture was extracted with ether the ether solution concentrated in vacuo The crude product was purified by chromatography on silica eluting with ethyl acetate-hexane (20:1)