4-[(2,2,2-trifluoroethylamino)methyl]benzonitrile

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

Procedure: Dissolve 4-[(2,2,2-trifluoroethylamino)-methyl]-benzonitrile (633 mg, 2.955 mmol) in methanol (22 mL). Add cobalt(II) chloride hexahydrate (1.41 g, 5.91 mmol) and stir for 20 min. Carefully add sodium borohydride (1.12 g, 29.55 mmol) in small batches and stir the mixture overnight. Quench the mixture with water and filter through celite, washing filtercake with chloroform:methanol:concentrated NH4OH (80:18:2). Concentrate the filtrate in vacuo, and partition the residue between water and chloroform. Extract the aqueous phase three times with chloroform iso-propanol (3:1). Dry the combined organic extracts over MgSO4, filter and concentrate in vacuo. Purify by chromatography on silica gel (40 g, pre-packed cartridge) eluting with DCM/(chloroform:methanol:concentrated NH4OH 80:18:2) (1:0 over 5 min, 19:1 over 5 min, 9:1 over 5 min, 85:15 over 5 min, 4:1; 50 mL/min) to obtain the title compound (316 mg, 49%). MS (ES+) m/z: 219 (M+H)+. Quench the mixture with water filter through celite washing filtercake with chloroform Concentrate the filtrate in vacuo partition the residue between water and chloroform Extract the aqueous phase three times with chloroform iso-propanol (3:1) Dry the combined organic extracts over MgSO4 filter concentrate in vacuo Purify by chromatography on silica gel (40 g, pre-packed cartridge) eluting with DCM/(chloroform:methanol:concentrated NH4OH 80:18:2) (1:0 over 5 min, 19:1 over 5 min, 9:1 over 5 min, 85:15 over 5 min, 4:1; 50 mL/min)

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

Procedure: Add sodium cyanoborohydride (957 mg, 15.24 mmol) to a stirred solution of 4-cyanobenzaldehyde (500 mg, 3.81 mmol), 2,2,2-trifluoroethylamine (0.3 mL, 3.81 mmol) and acetic acid (0.44 mL, 7.62 mmol) in methanol (5 mL). Stir the mixture overnight at room temperature. Partition the mixture between 1N aqueous NaOH and DCM. Extract the aqueous phase twice with DCM. Dry the combined organic extracts over MgSO4, filter and concentrate in vacuo to obtain the desired intermediate (749 mg, 92%) suitable for use without further purification. MS (ES+) m/z: 215 (M+H)+. Partition the mixture between 1N aqueous NaOH and DCM Extract the aqueous phase twice with DCM Dry the combined organic extracts over MgSO4 filter concentrate in vacuo