1-(3-bromopropyl)-4-chlorobenzene

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

Procedure: 1.83 g (15.1 mmol) of 3-ethyl-4-methylpyridine and 3.53 g (15.1 mmol) of 1-bromo-3-(4-chlorophenyl)-propane were reacted in the same manner as in Example 26. The reaction product was purified to obtain 2.33 g of the desired compound (yield: 56.3%). The reaction product was purified

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

Procedure: 1.83 g (15.1 mmol) of 3-ethyl-4-methylpyridine and 3.53 g (15.1 mmol) of 1-bromo-3-(4-chlorophenyl)-propane were reacted in the same manner as in Example 26. The reaction product was purified to obtain 2.33 g of the desired compound (yield: 56.3%). The reaction product was purified

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

Procedure: 3-(4-Chlorophenyl)-1-propanol (1.00 g) was dissolved in methylene chloride (30 ml), triphenylphosphine (1.66 g) and N-bromosuccinimide (1.11 g) were added under ice-cooling, and the mixture was stirred under ice-cooling for 6 hr. The reaction mixture was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. Diethyl ether (50 ml) was added, and the precipitated triphenylphosphine oxide was filtered off. The concentrate of the filtrate was purified by silica gel column chromatography (hexane alone) to give the object product (1.30 g) as a colorless oil. cooling cooling for 6 hr The reaction mixture was washed with water and saturated brine dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure Diethyl ether (50 ml) was added the precipitated triphenylphosphine oxide was filtered off The concentrate of the filtrate was purified by silica gel column chromatography (hexane alone)

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

Procedure: Using the procedure of Example 1, Step 2, the Grignard reagent prepared from 1-(3-bromopropyl)-4-chlorobenzene was added to the benzaldehyde of Step 1. The title compound so obtained was used as such in the next step.

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

Procedure: Prepared from 3-(4-chlorophenyl)propyl bromide and 2 equivalents of 2-amino-4,5,7,8-tetrahydro-6H-thiazolo[5,4-d]azepine in anhydrous dimethylformamide. Yield: 37% of theory, Melting point: 153° C.

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

Procedure: To a stirred solution of 4.15 g (15.8 mmol) of triphenylphosphine in 100 ml of toluene at 0° C., 1.51 ml (15.8 mmol) of bromine was added dropwise. This mixture was stirred for 3 hours then a solution of 3.90 g (22.9 mmol) of Part (a) alcohol and 1.63 ml (15.8 mmol) of pyridine in 20 ml of toluene was added. A solution of 25 ml hexane and 25 ml diethyl ether was added, and a brown mass was formed. The liquid was decanted and concentrated in vacuo. The residue was triturated with hexane:ethyl acetate and triphenylphosphine oxide was precipitated. The solid was filtered and the filtrate was concentrated in vacuo to give a yellow oil. The oil was purified by flash chromatography to obtain 1.80 g (7.72 mmol, 49%) of the desired product. a brown mass was formed The liquid was decanted concentrated in vacuo The residue was triturated with hexane ethyl acetate and triphenylphosphine oxide was precipitated The solid was filtered the filtrate was concentrated in vacuo to give a yellow oil The oil was purified by flash chromatography

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

Procedure: To a stirred solution of 4.15 g (15.8 mmol) of triphenylphosphine in 100 ml of toluene at 0° C., 1.51 ml (15.8 mmol) of bromine was added dropwise. This mixture was stirred for 3 hours then a solution of 3.90 g (22.9 mmol) of Part (a) alcohol and 1.63 ml (15.8 mmol) of pyridine in 20 ml of toluene was added. A solution of 25 ml hexane and 25 ml diethyl ether was added, and a brown mass was formed. The liquid was decanted and concentrated in vacuo. The residue was triturated with hexane:ethyl acetate and triphenylphosphine oxide was precipitated. The solid was filtered and the filtrate was concentrated in vacuo to give a yellow oil. The oil was purified by flash chromatography to obtain 1.80 g (7.72 mmol, 49%) of the desired product. a brown mass was formed The liquid was decanted concentrated in vacuo The residue was triturated with hexane ethyl acetate and triphenylphosphine oxide was precipitated The solid was filtered the filtrate was concentrated in vacuo to give a yellow oil The oil was purified by flash chromatography

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

Procedure: To a stirred solution of 4.15 g (15.8 mmol) of triphenylphosphine in 100 ml of toluene at 0° C., 1.51 ml (15.8 mmol) of bromine was added dropwise. This mixture was stirred for 3 hours then a solution of 3.90 g (22.9 mmol) of Part (a) alcohol and 1.63 ml (15.8 mmol) of pyridine in 20 ml of toluene was added. A solution of 25 ml hexane and 25 ml diethyl ether was added, and a brown mass was formed. The liquid was decanted and concentrated in vacuo. The residue was triturated with hexane:ethyl acetate and triphenylphosphine oxide was precipitated. The solid was filtered and the filtrate was concentrated in vacuo to give a yellow oil. The oil was purified by flash chromatography to obtain 1.80 g (7.72 mmol, 49%) of the desired product. a brown mass was formed The liquid was decanted concentrated in vacuo The residue was triturated with hexane ethyl acetate and triphenylphosphine oxide was precipitated The solid was filtered the filtrate was concentrated in vacuo to give a yellow oil The oil was purified by flash chromatography

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

Procedure: 1.83 g (15.1 mmol) of 3-ethyl-4-methylpyridine and 3.53 g (15.1 mmol) of 1-bromo-3-(4-chlorophenyl)-propane were reacted in the same manner as in Example 26. The reaction product was purified to obtain 2.33 g of the desired compound (yield: 56.3%). The reaction product was purified

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

Procedure: To a stirred solution of 4.15 g (15.8 mmol) of triphenylphosphine in 100 ml of toluene at 0° C., 1.51 ml (15.8 mmol) of bromine was added dropwise. This mixture was stirred for 3 hours then a solution of 3.90 g (22.9 mmol) of Part (a) alcohol and 1.63 ml (15.8 mmol) of pyridine in 20 ml of toluene was added. A solution of 25 ml hexane and 25 ml diethyl ether was added, and a brown mass was formed. The liquid was decanted and concentrated in vacuo. The residue was triturated with hexane:ethyl acetate and triphenylphosphine oxide was precipitated. The solid was filtered and the filtrate was concentrated in vacuo to give a yellow oil. The oil was purified by flash chromatography to obtain 1.80 g 7.72 mmol, 49%) of the desired product. a brown mass was formed The liquid was decanted concentrated in vacuo The residue was triturated with hexane ethyl acetate and triphenylphosphine oxide was precipitated The solid was filtered the filtrate was concentrated in vacuo to give a yellow oil The oil was purified by flash chromatography

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

Procedure: To a stirred solution of 4.15 g (15.8 mmol) of triphenylphosphine in 100 ml of toluene at 0° C., 1.51 ml (15.8 mmol) of bromine was added dropwise. This mixture was stirred for 3 hours then a solution of 3.90 g (22.9 mmol) of Part (a) alcohol and 1.63 ml (15.8 mmol) of pyridine in 20 ml of toluene was added. A solution of 25 ml hexane and 25 ml diethyl ether was added, and a brown mass was formed. The liquid was decanted and concentrated in vacuo. The residue was triturated with hexane:ethyl acetate and triphenylphosphine oxide was precipitated. The solid was filtered and the filtrate was concentrated in vacuo to give a yellow oil. The oil was purified by flash chromatography to obtain 1.80 g 7.72 mmol, 49%) of the desired product. a brown mass was formed The liquid was decanted concentrated in vacuo The residue was triturated with hexane ethyl acetate and triphenylphosphine oxide was precipitated The solid was filtered the filtrate was concentrated in vacuo to give a yellow oil The oil was purified by flash chromatography

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The potassium salt of phthalimide (4.4 g, 24 mmol) was dissolved in DMF (20 ml) and 1-chloro-4-(3-bromopropyl)benzene (4.67 g, 20 mmol) was added. The mixture was stirred at 80° C. for 16 hours. Water (50 ml) and DCM (50 ml) were added, the phases were separated and the aqueous phase extracted with DCM (2×50 ml). The combined organic phases were washed with sodium hydroxide (0.2 M, 50 ml), dried (magnesium sulphate), filtered and concentrated in vacuo. Ethanol (75 ml) and hydrazine hydrate (2 equiv.) were added and the mixture was heated to reflux for 2 hours. After cooling the mixture was filtrated and the filter cake washed with DCM (2×50 ml). The filtrate and washings were evaporated and dissolved in ethyl acetate (40 ml). Washing of the organic phase with sodium hydroxide (0.4 M, 2×25 ml) and water (2×25 ml) followed by drying (magnesium sulphate), filtration and evaporation gave 3-(4-chlorophenyl)propylamine. the phases were separated the aqueous phase extracted with DCM (2×50 ml) The combined organic phases were washed with sodium hydroxide (0.2 M, 50 ml) dried (magnesium sulphate) filtered concentrated in vacuo the mixture was heated to reflux for 2 hours After cooling the mixture was filtrated the filter cake washed with DCM (2×50 ml) The filtrate and washings were evaporated dissolved in ethyl acetate (40 ml) Washing of the organic phase with sodium hydroxide (0.4 M, 2×25 ml) and water (2×25 ml) by drying (magnesium sulphate), filtration and evaporation