2-[2-(trifluoromethoxy)phenyl]acetonitrile

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

Procedure: 2-(2-Trifluoromethoxy-benzyl)-4,5-dihydro-1H-imidazole was prepared from (2-trifluoromethoxy-phenyl)-acetonitrile and ethylene diamine in analogy to Example 19 b): yellow powder; MS (ISP): 245.0 ((M+H)+.).

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

Procedure: 2-(2-Trifluoromethoxy-benzyl)-4,5-dihydro-1H-imidazole was prepared from (2-trifluoromethoxy-phenyl)-acetonitrile and ethylene diamine in analogy to Example 19 b): yellow powder; MS (ISP): 245.0 ((M+H)+.).

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

Procedure: 2-Trifluoromethoxyphenylacetonitrile (0.49 g, 2.6 mmol) from Step 3 above was refluxed for 3 h in a 1:1 mixture of acetic acid and concentrated aqueous HCl. The solvents were removed under reduced pressure. The residue was partitioned between EtOAc (75 mL) and water (2×25 mL). The organic phase was separated, dried (MgSO4), filtered, and evaporated under reduced pressure to give 2-trifluoromethoxyphenylacetic acid as an amorphous solid (HPLC retention time=6.8 min (method A)). The solvents were removed under reduced pressure The residue was partitioned between EtOAc (75 mL) and water (2×25 mL) The organic phase was separated dried (MgSO4) filtered evaporated under reduced pressure

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

Procedure: To a stirred solution of 2-trifluoromethoxybenzyl bromide (0.95 g, 3.9 mmol) from Step 2 above in DMF (5 mL) was added NaCN (0.21 g, 4.3 mmol). The mixture was stirred at ambient temperature for 14 h and the solvent was removed under reduced pressure. The residue was purified by pressurized silica gel column chromatography using 15% EtOAc-hexanes as eluant to give 2-trifluoromethoxyphenylacetonitrile as a colorless liquid (TLC Rf =0.6 (solvent)). the solvent was removed under reduced pressure The residue was purified by pressurized silica gel column chromatography

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

Procedure: 2-Trifluoromethoxyphenylacetonitrile (0.49 g, 2.6 mmol) from Step 3 above was refluxed for 3 h in a 1:1 mixture of acetic acid and concentrated aqueous HCl. The solvents were removed under reduced pressure. The residue was partitioned between EtOAc (75 mL) and water (2×25 mL). The organic phase was separated, dried (MgSO4), filtered, and evaporated under reduced pressure to give 2-trifluoromethoxyphenylacetic acid as an amorphous solid (HPLC retention time=6.8 min (method A)). The solvents were removed under reduced pressure The residue was partitioned between EtOAc (75 mL) and water (2×25 mL) The organic phase was separated dried (MgSO4) filtered evaporated under reduced pressure

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

Procedure: To a stirred solution of 2-trifluoromethoxybenzyl bromide (0.95 g, 3.9 mmol) from Step 2 above in DMF (5 mL) was added NaCN (0.21 g, 4.3 mmol). The mixture was stirred at ambient temperature for 14 h and the solvent was removed under reduced pressure. The residue was purified by pressurized silica gel column chromatography using 15% EtOAc-hexanes as eluant to give 2-trifluoromethoxyphenylacetonitrile as a colorless liquid (TLC Rf =0.6 (solvent)). the solvent was removed under reduced pressure The residue was purified by pressurized silica gel column chromatography

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

Procedure: 2-Trifluoromethoxyphenylacetonitrile (0.49 g, 2.6 mmol) from Step 3 above was refluxed for 3 h in a 1:1 mixture of acetic acid and concentrated aqueous HCl. The solvents were removed under reduced pressure. The residue was partitioned between EtOAc (75 mL) and water (2×25 mL). The organic phase was separated, dried (MgSO4), filtered, and evaporated under reduced pressure to give 2-trifluoromethoxyphenylacetic acid as an amorphous solid (HPLC retention time=6.8 min (method A)). The solvents were removed under reduced pressure The residue was partitioned between EtOAc (75 mL) and water (2×25 mL) The organic phase was separated dried (MgSO4) filtered evaporated under reduced pressure

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

Procedure: To a stirred solution of 2-trifluoromethoxybenzyl bromide (0.95 g, 3.9 mmol) from Step 2 above in DMF (5 mL) was added NaCN (0.21 g, 4.3 mmol). The mixture was stirred at ambient temperature for 14 h and the solvent was removed under reduced pressure. The residue was purified by pressurized silica gel column chromatography using 15% EtOAc-hexanes as eluant to give 2-trifluoromethoxyphenylacetonitrile as a colorless liquid (TLC Rf =0.6 (solvent)). the solvent was removed under reduced pressure The residue was purified by pressurized silica gel column chromatography

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

Procedure: 2-(2-Trifluoromethoxy-benzyl)-4,5-dihydro-1H-imidazole was prepared from (2-trifluoromethoxy-phenyl)-acetonitrile and ethylene diamine in analogy to Example 19 b): yellow powder; MS (ISP): 245.0 ((M+H)+.).