4-(2-Bromoethyl)benzonitrile

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: A solution of phosphorus tribromide (5 g) in carbon tetrachloride (10 ml) was added, dropwise, to a solution of 4-cyanophenethyl alcohol (8.06 g) in carbon tetrachloride (60 ml). The mixture was heated under reflux for 4 hours. On cooling to room temperature, the mixture was poured onto ice (200 g). The layers were separated and the organic layer was washed with 10% aqueous sodium carbonate (50 ml) and brine (50 ml), dried (MgSO4) and concentrated in vacuo to give a colourless oil which solidified on standing. The solid was chromatographed on silica eluting with ethyl acetate containing hexane (20%). The fractions containing the less polar (higher Rf) product were combined and concentrated in vacuo to give 4-cyanophenethyl bromide as a yellow oil which solidified on standing, yield 8.9 g. The fractions containing the more polar (lower Rf) product were combined and concentrated in vacuo to give the title compound as a colourless solid, yield 0.47 g, m.p. 152°-153° . The mixture was heated under reflux for 4 hours the mixture was poured onto ice (200 g) The layers were separated the organic layer was washed with 10% aqueous sodium carbonate (50 ml) and brine (50 ml) dried (MgSO4) concentrated in vacuo to give a colourless oil which The solid was chromatographed on silica eluting with ethyl acetate containing hexane (20%) The fractions containing the less polar (higher Rf) product concentrated in vacuo

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: A solution of phosphorus tribromide (5 g) in carbon tetrachloride (10 ml) was added, dropwise, to a solution of 4-cyanophenethyl alcohol (8.06 g) in carbon tetrachloride (60 ml). The mixture was heated under reflux for 4 hours. On cooling to room temperature, the mixture was poured onto ice (200 g). The layers were separated and the organic layer was washed with 10% aqueous sodium carbonate (50 ml) and brine (50 ml), dried (MgSO4) and concentrated in vacuo to give a colourless oil which solidified on standing. The solid was chromatographed on silica eluting with ethyl acetate containing hexane (20%). The fractions containing the less polar (higher Rf) product were combined and concentrated in vacuo to give 4-cyanophenethyl bromide as a yellow oil which solidified on standing, yield 8.9 g. The fractions containing the more polar (lower Rf) product were combined and concentrated in vacuo to give the title compound as a colourless solid, yield 0.47 g, m.p. 152°-153° . The mixture was heated under reflux for 4 hours the mixture was poured onto ice (200 g) The layers were separated the organic layer was washed with 10% aqueous sodium carbonate (50 ml) and brine (50 ml) dried (MgSO4) concentrated in vacuo to give a colourless oil which The solid was chromatographed on silica eluting with ethyl acetate containing hexane (20%) The fractions containing the less polar (higher Rf) product concentrated in vacuo

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

Procedure: Combined 4-(2-bromoethyl)benzonitrile (68 mg, 0.32 mmol) with 1-(piperazin-1-yl)-2-[4-(1H-tetrazol-1-yl)phenyl]ethanone hydrochloride (100 mg, 0.324 mmol), tetrabutyl ammonium iodide (120 mg, 0.324 mmol) and potassium carbonate (179 mg, 1.30 mmol) in DMF (2 mL) and stirred at 80° C. overnight. The reaction mixture was poured into water and extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated. After initial purification by HPLC, repurification by preparative TLC eluting with 5% of 1:9 NH4OH/methanol in DCM afforded the title compound. LC/MS: [(M+1)]+=402. extracted twice with ethyl acetate The combined organic layers were washed with brine dried over MgSO4 filtered concentrated After initial purification by HPLC, repurification by preparative TLC eluting with 5% of 1:9 NH4OH/methanol in DCM

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

Procedure: 4-(2Hydroxyethyl)benzonitrile (3.0 g, 20 mmol) was combined with triphenylphosphine (6.42 g, 24.5 mmol) imidazole (1.39 g, 20.4 mmol) and carbon tetrabromide (8.11 g, 24.5 mmol) in DCM (10 mL) and stirred at 0° C., monitoring the reaction progress to completion by TLC. Silica gel was added to the mixture and the solvent was removed. Purification by MPLC eluting with 20% ethyl acetate/hexanes afforded the tide compound. Silica gel was added to the mixture the solvent was removed Purification by MPLC eluting with 20% ethyl acetate/hexanes afforded the tide compound