1-(4-Bromophenoxy)propane

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

Procedure: A mixture of 4-bromophenol (8.65 g), potassium iodide (83 mg), potassium carbonate (6.9 g) and propyl bromide (6.15 g) was heated under reflux in acetone (100 ml) for 48 hours. The reaction was cooled to ambient temperature, filtered and the acetone removed in vacuo to give an amber oil. This was purified by gradient elution with 20% ethyl acetate/isohexane through a silica gel Mega Bond Elut column to give 1-bromo-4-propoxybenzene (9.4 g) as a clear oil, mass spectrum (+ve CI): 214 (M+H)+. was heated filtered the acetone removed in vacuo to give an amber oil This was purified by gradient elution with 20% ethyl acetate/isohexane through a silica gel Mega Bond Elut column

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

Procedure: A mixture of 4-bromophenol (8.65 g), potassium iodide (83 mg), potassium carbonate (6.9 g) and propyl bromide (6.15 g) was heated under reflux in acetone (100 ml) for 48 hours. The reaction was cooled to ambient temperature, filtered and the acetone removed in vacuo to give an amber oil. This was purified by gradient elution with 20% ethyl acetate/isohexane through a silica gel Mega Bond Elut column to give 1-bromo-4-propoxybenzene (9.4 g) as a clear oil, mass spectrum (+ve CI): 214 (M+H)+. was heated filtered the acetone removed in vacuo to give an amber oil This was purified by gradient elution with 20% ethyl acetate/isohexane through a silica gel Mega Bond Elut column

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

Procedure: The title compound was prepared following the procedure of Intermediate 17, but starting from 1-bromo-4-propoxybenzene. Purification by chromatography (DCM/MeOH 80/20) afforded the title compound as a brown oil (34%). HPLC (Condition A), Rt: 1.9 min (HPLC purity: 80.2%). M+(ESI): 235.2 The title compound was prepared Purification by chromatography (DCM/MeOH 80/20)

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

Procedure: The title compound was prepared following the procedure of Intermediate 17, but starting from 1-bromo-4-propoxybenzene. Purification by chromatography (DCM/MeOH 80/20) afforded the title compound as a brown oil (34%). HPLC (Condition A), Rt: 1.9 min (HPLC purity: 80.2%). M+(ESI): 235.2 The title compound was prepared Purification by chromatography (DCM/MeOH 80/20)

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

Procedure: Prepare a solution of 4-bromo-phenol (17.30 g, 0.10 mol) and potassium carbonate (13.80 g, 0.1 mole) in isopropanol (175 mL). Heat the resulting mixture at reflux and stir overnight. Cool to ambient temperature, filter and condense the filtrate on a rotary evaporator. Dissolve the residual oil in ethyl acetate (250 mL) and extract twice with 5% sodium hydroxide (100 mL), separate and wash with brine. Kugelrohr distillation at 100°-120°, 0.05 mm, gives the title compound (12.86 g, 60%) as a clear liquid. Heat the resulting mixture at reflux filter condense the filtrate on a rotary evaporator Dissolve the residual oil in ethyl acetate (250 mL) extract twice with 5% sodium hydroxide (100 mL) separate wash with brine Kugelrohr distillation at 100°-120°

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

Procedure: In 100 ml of dimethylsulfoxide was dissolved 17.3 g (100.0 mmol) of 4-bromophenol, and an aqueous solution of sodium hydroxide (NaOH/H2O: 4.0 g/25 ml) was added thereto. The resultant mixture was stirred until dissolving homogeneously. Next was added 12.3 g (100.0 mmol) of n-propyl bromide to the resultant mixture, and the reaction was carried out at a room temperature for 24 hours. The reaction mixture was poured into an iced water, and the resultant oil was extracted with hexane. After the hexane phase was washed with water, hexane was removed from the hexane phase to give 20.5 g (95.3 mmol) of 1-bromo-4-n-propyloxybenzene. until dissolving homogeneously the resultant oil was extracted with hexane After the hexane phase was washed with water, hexane was removed from the hexane phase

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

Procedure: A mixture of 4-bromophenol (8.65 g), potassium iodide (83 mg), potassium carbonate (6.9 g) and propyl bromide (6.15 g) was heated under reflux in acetone (100 ml) for 48 hours. The reaction was cooled to ambient temperature, filtered and the acetone removed in vacuo to give an amber oil. This was purified by gradient elution with 20% ethyl acetate/isohexane through a silica gel Mega Bond Elut column to give 1-bromo-4-propoxybenzene (9.4 g) as a clear oil, mass spectrum (+ve CI): 214 (M+H)+. was heated filtered the acetone removed in vacuo to give an amber oil This was purified by gradient elution with 20% ethyl acetate/isohexane through a silica gel Mega Bond Elut column

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazole (152 mg, 0.8 mmol), 1-bromo-4-(propyloxy)benzene (177 mg, 0.8 mmol), N,N-dimethylglycine (16 mg, 0.16 mmol), copper (I) iodide (16 mg, 0.08 mmol), potassium carbonate (235 mg, 1.7 mmol) in dimethylsulfoxide (3 ml) was heated in a microwave reactor at 180° C. for a total of 50 minutes. Fresh N,N-dimethylglycine (16 mg, 0.16 mmol) and copper (I) iodide (16 mg, 0.08 mmol) was added and heating continued at 180° C. for a further 30 minutes. The reaction mixture was then filtered through a 5 g sep-pack column with 40 ml 1:1 ethyl acetate in petroleum ether. The solvent was removed by rotary evaporation and the residue partitioned between ethyl acetate (20 ml) and water (20 ml). The organic layer was retained and washed with brine (2×10 ml), then dried over sodium sulphate. The solvent was removed by rotary evaporation and the sample purified by MDAP. The relevant fractions were combined and the solvent removed by rotary evaporation to give the title compound (23 mg, 9%). heating The reaction mixture was then filtered through a 5 g sep-pack column with 40 ml 1:1 ethyl acetate in petroleum ether The solvent was removed by rotary evaporation the residue partitioned between ethyl acetate (20 ml) and water (20 ml) washed with brine (2×10 ml) dried over sodium sulphate The solvent was removed by rotary evaporation the sample purified by MDAP the solvent removed by rotary evaporation

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazole (152 mg, 0.8 mmol), 1-bromo-4-(propyloxy)benzene (177 mg, 0.8 mmol), N,N-dimethylglycine (16 mg, 0.16 mmol), copper (I) iodide (16 mg, 0.08 mmol), potassium carbonate (235 mg, 1.7 mmol) in dimethylsulfoxide (3 ml) was heated in a microwave reactor at 180° C. for a total of 50 minutes. Fresh N,N-dimethylglycine (16 mg, 0.16 mmol) and copper (I) iodide (16 mg, 0.08 mmol) was added and heating continued at 180° C. for a further 30 minutes. The reaction mixture was then filtered through a 5 g sep-pack column with 40 ml 1:1 ethyl acetate in petroleum ether. The solvent was removed by rotary evaporation and the residue partitioned between ethyl acetate (20 ml) and water (20 ml). The organic layer was retained and washed with brine (2×10 ml), then dried over sodium sulphate. The solvent was removed by rotary evaporation and the sample purified by MDAP. The relevant fractions were combined and the solvent removed by rotary evaporation to give the title compound (23 mg, 9%). heating The reaction mixture was then filtered through a 5 g sep-pack column with 40 ml 1:1 ethyl acetate in petroleum ether The solvent was removed by rotary evaporation the residue partitioned between ethyl acetate (20 ml) and water (20 ml) washed with brine (2×10 ml) dried over sodium sulphate The solvent was removed by rotary evaporation the sample purified by MDAP the solvent removed by rotary evaporation

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazole (152 mg, 0.8 mmol), 1-bromo-4-(propyloxy)benzene (177 mg, 0.8 mmol), N,N-dimethylglycine (16 mg, 0.16 mmol), copper (I) iodide (16 mg, 0.08 mmol), potassium carbonate (235 mg, 1.7 mmol) in dimethylsulfoxide (3 ml) was heated in a microwave reactor at 180° C. for a total of 50 minutes. Fresh N,N-dimethylglycine (16 mg, 0.16 mmol) and copper (I) iodide (16 mg, 0.08 mmol) was added and heating continued at 180° C. for a further 30 minutes. The reaction mixture was then filtered through a 5 g sep-pack column with 40 ml 1:1 ethyl acetate in petroleum ether. The solvent was removed by rotary evaporation and the residue partitioned between ethyl acetate (20 ml) and water (20 ml). The organic layer was retained and washed with brine (2×10 ml), then dried over sodium sulphate. The solvent was removed by rotary evaporation and the sample purified by MDAP. The relevant fractions were combined and the solvent removed by rotary evaporation to give the title compound (23 mg, 9%). heating The reaction mixture was then filtered through a 5 g sep-pack column with 40 ml 1:1 ethyl acetate in petroleum ether The solvent was removed by rotary evaporation the residue partitioned between ethyl acetate (20 ml) and water (20 ml) washed with brine (2×10 ml) dried over sodium sulphate The solvent was removed by rotary evaporation the sample purified by MDAP the solvent removed by rotary evaporation

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

Procedure: The title compound was prepared following the procedure of Intermediate 17, but starting from 1-bromo-4-propoxybenzene. Purification by chromatography (DCM/MeOH 80/20) afforded the title compound as a brown oil (34%). HPLC (Condition A), Rt: 1.9 min (HPLC purity: 80.2%). M+(ESI): 235.2 The title compound was prepared Purification by chromatography (DCM/MeOH 80/20)

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

Procedure: A mixture of 4-bromophenol (8.65 g), potassium iodide (83 mg), potassium carbonate (6.9 g) and propyl bromide (6.15 g) was heated under reflux in acetone (100 ml) for 48 hours. The reaction was cooled to ambient temperature, filtered and the acetone removed in vacuo to give an amber oil. This was purified by gradient elution with 20% ethyl acetate/isohexane through a silica gel Mega Bond Elut column to give 1-bromo-4-propoxybenzene (9.4 g) as a clear oil, mass spectrum (+ve CI): 214 (M+H)+. was heated filtered the acetone removed in vacuo to give an amber oil This was purified by gradient elution with 20% ethyl acetate/isohexane through a silica gel Mega Bond Elut column