2-(2-chlorophenyl)-N-methylacetamide

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: At 0° C., a solution of iodine (29.9 g, 0.12 mol) in THF (100 ml) was added dropwise to a suspension of sodium borohydride (11.1 g, 0.29 mol) and 2-(2-chlorophenyl)-N-methylacetamide (21.6 g, 0.12 mol) in THF (150 ml). After the addition was completed, the reaction mixture was heated to reflux for 16 hours. It was cooled to 0° C. Methanol (150 ml) was added dropwise. The solvent was removed in vacuo. The residue was dissolved in a mixture of tert-butyl methyl ether (200 ml) and a 20% aqueous solution of sodium hydroxide (200 ml). The phases were separated. The aqueous phase was extracted with tert-butyl methyl ether (2×100 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 (300 g), using a mixture of DCM/methanol/25% aqueous ammonia (first: 100:10:1, then: 100:20:2, then 100:30:3) as eluent, to give 3.82 g of N-[2-(2-chlorophenyl)ethyl]-N-methylamine. After the addition the reaction mixture was heated to reflux for 16 hours The solvent was removed in vacuo The residue was dissolved in a mixture of tert-butyl methyl ether (200 ml) The phases were separated The aqueous phase was extracted with tert-butyl methyl ether (2×100 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 (300 g) a mixture of DCM/methanol/25% aqueous ammonia (first: 100:10:1

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: At 0° C., 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (28.1 g, 0.15 mol) was added to a solution of 1-hydroxybenzotriazole (19.8 g, 0.15 mol) and 2-chlorophenylacetic acid (Aldrich 19,063-2, 25.0 g, 0.15 mol) in N,N-dimethylformamide (150 ml) and DCM (50 ml). The reaction mixture was stirred for 20 min at 0° C. A 33% solution of methylamine in ethanol (365 ml, 2.9 mol) was added. The reaction mixture was stirred for 56 hours at room temperature. It was diluted with ethyl acetate (300 ml) and washed with a 10% aqueous solution of sodium hydrogensulphate (400 ml). The aqueous phase was extracted with ethyl acetate (2×150 ml). The combined organic layers were washed with a saturated solution of sodium hydrogencarbonate (400 ml) and dried over magnesium sulphate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (300 g), using ethyl acetate/heptane 2:1 as eluent, to give 21.6 g of 2-(2-chlorophenyl)-N-methylacetamide. The reaction mixture was stirred for 56 hours at room temperature washed with a 10% aqueous solution of sodium hydrogensulphate (400 ml) The aqueous phase was extracted with ethyl acetate (2×150 ml) The combined organic layers were washed with a saturated solution of sodium hydrogencarbonate (400 ml) dried over magnesium sulphate The solvent was removed in vacuo The crude product was purified by flash chromatography on silica (300 g)

反応条件: temp:0.00; pressure:0.00; stir: