4-(4-chlorophenyl)-N-methylbutan-1-amine

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: At 0° C., a solution of of 4-(4-chlorophenyl)-N-methylbutyramide (3.80 g, 18.0 mmol) in tetrahydrofuran (60 ml) was added to a suspension of sodium borohydride (1.60 g, 43.1 mmol) in THF (60 ml). The mixture was stirred for 20 min at 0° C. A solution of iodine (4.6 g, 18.0 mmol) in THF (100 ml) was added dropwise. After the addition was finished, the reaction mixture was warmed to 70° C. It was stirred for 16 hours at this temperature. It was cooled to 0° C. Methanol (100 ml) was added dropwise. The solvents were removed in vacuo. The residue was dissolved in a 20% aqueous solution of sodium hydroxide (160 ml) and tert-butyl methyl ether (200 ml). The phases were separated. The aqueous phase was extracted with tert-butyl methyl ether (3×70 ml). The combined organic layers were dried over magnesium sulphate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (90 g), using DCM/methanol/25% aqueous ammonia as eluent, to give 820 mg of N-[4-(4-chlorophenyl)butyl]-N-methylamine. After the addition the reaction mixture was warmed to 70° C It was stirred for 16 hours at this temperature It was cooled to 0° C The solvents were removed in vacuo The residue was dissolved in a 20% aqueous solution of sodium hydroxide (160 ml) and tert-butyl methyl ether (200 ml) The phases were separated The aqueous phase was extracted with tert-butyl methyl ether (3×70 ml) The combined organic layers were dried over magnesium sulphate The solvent was removed in vacuo The crude product was purified by flash chromatography on silica (90 g)

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

Procedure: At 0° C., a solution of of 4-(4-chlorophenyl)-N-methylbutyramide (3.80 g, 18.0 mmol) in tetrahydrofuran (60 ml) was added to a suspension of sodium borohydride (1.60 g, 43.1 mmol) in THF (60 ml). The mixture was stirred for 20 min at 0° C. A solution of iodine (4.6 g, 18.0 mmol) in THF (100 ml) was added dropwise. After the addition was finished, the reaction mixture was warmed to 70° C. It was stirred for 16 hours at this temperature. It was cooled to 0° C. Methanol (100 ml) was added dropwise. The solvents were removed in vacuo. The residue was dissolved in a 20% aqueous solution of sodium hydroxide (160 ml) and tert-butyl methyl ether (200 ml). The phases were separated. The aqueous phase was extracted with tert-butyl methyl ether (3×70 ml). The combined organic layers were dried over magnesium sulphate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (90 g), using DCM/methanol/25% aqueous ammonia as eluent, to give 820 mg of N-[4-(4-chlorophenyl)butyl]-N-methylamine. After the addition the reaction mixture was warmed to 70° C It was stirred for 16 hours at this temperature It was cooled to 0° C The solvents were removed in vacuo The residue was dissolved in a 20% aqueous solution of sodium hydroxide (160 ml) and tert-butyl methyl ether (200 ml) The phases were separated The aqueous phase was extracted with tert-butyl methyl ether (3×70 ml) The combined organic layers were dried over magnesium sulphate The solvent was removed in vacuo The crude product was purified by flash chromatography on silica (90 g)