4-BROMO-1-CHLORO-2-ETHYLBENZENE

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

Procedure: In analogy to the procedure described for the synthesis example 71 (step 1), the title compound (4-chloro-3-ethyl-phenyl)-[2-(5-trifluoromethyl-pyridin-2-yl)-ethyl]-amine (MS m/e: 329.2 [M+H]+) was prepared from 4-bromo-1-chloro-2-ethylbenzene instead of 6-bromo-2,3-dihydro-benzofuran and 2-(5-trifluoromethyl-pyridin-2-yl)-ethylamine instead of 2-(6-trifluoromethyl-pyridin-3-yl)-ethylamine. In analogy to the procedure described for the synthesis example 71 (step 1)

Conditions: temp:170.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium hydroxide (0.39 g, 9.6 mmol) and hydrazine monohydrate (0.56 mL, 11.5 mmol) were added to a solution of 1-(5-Bromo-2-chloro-phenyl)-ethanone (0.9 g, 3.85 mmol) dissolved in triethylene glycol (5 mL). The reaction mixture was heated to 170° C. for 24 hours and then partitioned between 1N HCl and EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated. The residue was purified by flash silica gel chromatography (0% to 5% EtOAc in hexanes) to give the title compound (0.52 g, 62%). 1H NMR (400 MHz, CDCl3): δ 1.23 (t, J=7.6 Hz, 3 H), 2.72 (q, J=7.6 Hz, 2 H), 7.19 (d, J=8.6 Hz, 1 H), 7.25 (dd, J=8.3, 2.3 Hz, 1 H), 7.36 (d, J=2.5 Hz, 1 H). partitioned between 1N HCl and EtOAc The organic layer was washed with brine dried over Na2SO4 concentrated The residue was purified by flash silica gel chromatography (0% to 5% EtOAc in hexanes)

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

Procedure: To a solution of 4.319 g of 4-bromo-1-chloro-2-ethyl-benzene (20 mmol) in 50 ml diethylether, cooled to 0° C., were added dropwise 12.3 ml of 1.6M n-BuLi in hexane. After 30 min. stirring at 0° C. and 2 h at RT, a solution of 2.43 ml DMF (31 mmol) in 10 ml diethylether was added dropwise (temperature raised from 20 to 28° C.). After 1 h additional stirring at RT, the reaction mixture was acidified with 2N HCl, diluted with 150 ml water and extracted with diethylether. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered off and concentrated in vacuo. The residue was purified by flash column chromatography (heptane/AcOEt: 95/5) to yield 2.1 g of a colorless oil. MS (ISP) 168.1 (M+H)+. (temperature raised from 20 to 28° C.) After 1 h additional stirring at RT extracted with diethylether The combined organic layers were washed with brine dried over magnesium sulfate filtered off concentrated in vacuo The residue was purified by flash column chromatography (heptane/AcOEt: 95/5)

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

Procedure: To a solution of 4.319 g of 4-bromo-1-chloro-2-ethyl-benzene (20 mmol) in 50 ml diethylether, cooled to 0° C., were added dropwise 12.3 ml of 1.6M n-BuLi in hexane. After 30 min. stirring at 0° C. and 2 h at RT, a solution of 2.43 ml DMF (31 mmol) in 10 ml diethylether was added dropwise (temperature raised from 20 to 28° C.). After 1 h additional stirring at RT, the reaction mixture was acidified with 2N HCl, diluted with 150 ml water and extracted with diethylether. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered off and concentrated in vacuo. The residue was purified by flash column chromatography (heptane/AcOEt: 95/5) to yield 2.1 g of a colorless oil. MS (ISP) 168.1 (M+H)+. (temperature raised from 20 to 28° C.) After 1 h additional stirring at RT extracted with diethylether The combined organic layers were washed with brine dried over magnesium sulfate filtered off concentrated in vacuo The residue was purified by flash column chromatography (heptane/AcOEt: 95/5)

Conditions: temp:170.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium hydroxide (0.39 g, 9.6 mmol) and hydrazine monohydrate (0.56 mL, 11.5 mmol) were added to a solution of 1-(5-Bromo-2-chloro-phenyl)-ethanone (0.9 g, 3.85 mmol) dissolved in triethylene glycol (5 mL). The reaction mixture was heated to 170° C. for 24 hours and then partitioned between 1N HCl and EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated. The residue was purified by flash silica gel chromatography (0% to 5% EtOAc in hexanes) to give the title compound (0.52 g, 62%). 1H NMR (400 MHz, CDCl3): δ 1.23 (t, J=7.6 Hz, 3H), 2.72 (q, J=7.6 Hz, 2H), 7.19 (d, J=8.6 Hz, 1H), 7.25 (dd, J=8.3, 2.3 Hz, 1H), 7.36 (d, J=2.5 Hz, 1H). partitioned between 1N HCl and EtOAc The organic layer was washed with brine dried over Na2SO4 concentrated The residue was purified by flash silica gel chromatography (0% to 5% EtOAc in hexanes)

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

Procedure: In analogy to the procedure described for the synthesis example 71 (step 1), the title compound (4-chloro-3-ethyl-phenyl)-[2-(5-trifluoromethyl-pyridin-2-yl)-ethyl]-amine (MS m/e: 329.2 [M+H]+) was prepared from 4-bromo-1-chloro-2-ethylbenzene instead of 6-bromo-2,3-dihydro-benzofuran and 2-(5-trifluoromethyl-pyridin-2-yl)-ethylamine instead of 2-(6-trifluoromethyl-pyridin-3-yl)-ethylamine. In analogy to the procedure described for the synthesis example 71 (step 1)

Conditions: temp:170.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium hydroxide (0.39 g, 9.6 mmol) and hydrazine monohydrate (0.56 mL, 11.5 mmol) were added to a solution of 1-(5-Bromo-2-chloro-phenyl)-ethanone (0.9 g, 3.85 mmol) dissolved in triethylene glycol (5 mL). The reaction mixture was heated to 170° C. for 24 hours and then partitioned between 1N HCl and EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated. The residue was purified by flash silica gel chromatography (0% to 5% EtOAc in hexanes) to give the title compound (0.52 g, 62%). 1H NMR (400 MHz, CDCl3): δ 1.23 (t, J=7.6 Hz, 3 H), 2.72 (q, J=7.6 Hz, 2 H), 7.19 (d, J=8.6 Hz, 1 H), 7.25 (dd, J=8.3, 2.3 Hz, 1 H), 7.36 (d, J=2.5 Hz, 1 H). partitioned between 1N HCl and EtOAc The organic layer was washed with brine dried over Na2SO4 concentrated The residue was purified by flash silica gel chromatography (0% to 5% EtOAc in hexanes)

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

Procedure: To a solution of 4.319 g of 4-bromo-1-chloro-2-ethyl-benzene (20 mmol) in 50 ml diethylether, cooled to 0° C., were added dropwise 12.3 ml of 1.6M n-BuLi in hexane. After 30 min. stirring at 0° C. and 2 h at RT, a solution of 2.43 ml DMF (31 mmol) in 10 ml diethylether was added dropwise (temperature raised from 20 to 28° C.). After 1 h additional stirring at RT, the reaction mixture was acidified with 2N HCl, diluted with 150 ml water and extracted with diethylether. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered off and concentrated in vacuo. The residue was purified by flash column chromatography (heptane/AcOEt: 95/5) to yield 2.1 g of a colorless oil. MS (ISP) 168.1 (M+H)+. (temperature raised from 20 to 28° C.) After 1 h additional stirring at RT extracted with diethylether The combined organic layers were washed with brine dried over magnesium sulfate filtered off concentrated in vacuo The residue was purified by flash column chromatography (heptane/AcOEt: 95/5)