2-bromo-1,3,4-trifluorobenzene

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:; See reaction.notes.procedure_details.

Procedure: To a solution of 1.21 g of 4-ethylaniline, 1.10 g of 2,3,6-trifluoro-bromobenzene in 10 g of toluene is added consecutively 350 mg BINAP and 300 mg of bis-dibenzylideneaceton-palladium (0) [Pd(dba)2) in 3 ml of toluene and 0.9 g of sodium tert.-butoxide in 3 ml toluene. The mixture is flushed with nitrogen and heated for 6 h under reflux. After cooling to room temperature, water (30 ml), concentrated hydrochloric acid (10 ml) and hyflo (1 g) are added and stirring is continued for 1 h. The mixture is filtered and the filtrate is separated into its phases. The organic phase is washed three times with water, dried using magnesium sulfate and evaporated to dryness. The residue can be used as such in the following step or purified by flash chromatography on silica using toluene as the eluent affording 1.13 g of N-(2′,3′,6′-trifluorophenyl)-4-ethylanilin. The mixture is flushed with nitrogen heated for 6 h under reflux water (30 ml), concentrated hydrochloric acid (10 ml) and hyflo (1 g) are added The mixture is filtered the filtrate is separated into its phases The organic phase is washed three times with water dried evaporated to dryness purified by flash chromatography on silica

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

Procedure: To a solution of 1.21 g of 4-ethylaniline, 1.10 g of 2,3,6-trifluoro-bromobenzene in 10 g of toluene is added consecutively 350 mg BINAP and 300 mg of bis-dibenzylideneaceton-palladium (0) [Pd(dba)2) in 3 ml of toluene and 0.9 g of sodium tert.-butoxide in 3 ml toluene. The mixture is flushed with nitrogen and heated for 6 h under reflux. After cooling to room temperature, water (30 ml), concentrated hydrochloric acid (10 ml) and hyflo (1 g) are added and stirring is continued for 1 h. The mixture is filtered and the filtrate is separated into its phases. The organic phase is washed three times with water, dried using magnesium sulfate and evaporated to dryness. The residue can be used as such in the following step or purified by flash chromatography on silica using toluene as the eluent affording 1.13 g of N-(2′,3′,6′-trifluorophenyl)-4-ethylanilin. The mixture is flushed with nitrogen heated for 6 h under reflux water (30 ml), concentrated hydrochloric acid (10 ml) and hyflo (1 g) are added The mixture is filtered the filtrate is separated into its phases The organic phase is washed three times with water dried evaporated to dryness purified by flash chromatography on silica

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

Procedure: Couple trifluoromethanesulfonic acid 6-methoxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl ester (1.81 g, 3.37 mmol) with 2-bromo-1,3,4-trifluoro-benzene (1.42 g, 6.75 mmol) in a procedure similar to the preparation of [6-hydroxy-2-(2,3,5-trifluoro-phenyl)-naphthalen-1-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone to give 0.79 g (45%) of the title compound: mass spectrum (ion spray): m/z=520.3 (M+1).

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

Procedure: Couple trifluoromethanesulfonic acid 1-[4-(2-azepan-1-yl-ethoxy)-benzoyl]-6-methoxynaphthalen-2-yl ester (1.48 g, 2.67 mmol) with 2-bromo-1,3,4-trifluoro-benzene (1.13 g, 5.35 mmol) in a procedure similar to the preparation of [6-hydroxy-2-(2,3,5-trifluoro-phenyl)-naphthalen-1-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone to give 660 mg (46%) of the title compound: mass spectrum (ion spray): m/z=534.4 (M+H).

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

Procedure: Couple trifluoromethanesulfonic acid 1-[4-(2-azepan-1-yl-ethoxy)-benzoyl]-6-methoxynaphthalen-2-yl ester (1.48 g, 2.67 mmol) with 2-bromo-1,3,4-trifluoro-benzene (1.13 g, 5.35 mmol) in a procedure similar to the preparation of [6-hydroxy-2-(2,3,5-trifluoro-phenyl)-naphthalen-1-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone to give 0.66 g (46%) of the title compound: mass spectrum (ion spray) m/z=534.4 (M+H).

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

Procedure: Couple trifluoromethanesulfonic acid 6-methoxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl ester (1.81 g, 3.37 mmol) with 2-bromo-1,3,4-trifluoro-benzene (1.42 g, 6.75 mmol) in a procedure similar to the preparation of 6-hydroxy-2-(2,3,5-trifluoro-phenyl)-naphthalen-1-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone to give 0.79 g (45%) of the title compound: mass spectrum (ion spray) m/z=520.3 (M+H).

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

Procedure: To a solution of 1.21 g of 4-ethylaniline, 1.10 g of 2,3,6-trifluoro-bromobenzene in 10 g of toluene is added consecutively 350 mg BINAP and 300 mg of bis-dibenzylideneaceton-palladium (0) [Pd(dba)2) in 3 ml of toluene and 0.9 g of sodium tert.-butoxide in 3 ml toluene. The mixture is flushed with nitrogen and heated for 6 h under reflux. After cooling to room temperature, water (30 ml), concentrated hydrochloric acid (10 ml) and hyflo (1 g) are added and stirring is continued for 1 h. The mixture is filtered and the filtrate is separated into its phases. The organic phase is washed three times with water, dried using magnesium sulfate and evaporated to dryness. The residue can be used as such in the following step or purified by flash chromatography on silica using toluene as the eluent affording 1.13 g of N-(2′,3′,6′-trifluorophenyl)-4-ethylanilin. The mixture is flushed with nitrogen heated for 6 h under reflux water (30 ml), concentrated hydrochloric acid (10 ml) and hyflo (1 g) are added The mixture is filtered the filtrate is separated into its phases The organic phase is washed three times with water dried evaporated to dryness purified by flash chromatography on silica