2-(2-hydroxyphenyl)-N-methylacetamide

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

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

Procedure: Potassium carbonate (2.81 g, 20.34 mmol) was given to a solution of 2-(2-hydroxyphenyl)-N-methylacetamide (3.36 g, 20.34 mmol) in acetone (150 ml). Ethyl bromoacetate (2.13 ml, 19.32 mmol) and potassium iodide (166 mg, 1.02 mmol) were added successively. The reaction mixture was heated to reflux for 6 h. It was left at room temperature for 16 h. The solid was filtered off. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (80 g), using ethyl acetate/dichloromethane (1:1) as eluent, to give 5.00 g of ethyl 2-(2-((N-methylcarbamoyl)methyl)phenoxy)acetate. The reaction mixture was heated to reflux for 6 h The solid was filtered off The solvent was removed in vacuo The crude product was purified by flash chromatography on silica (80 g)

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

Procedure: (2-Hydroxyphenyl)acetic acid (9.89 g, 63.7 mmol) and 1-hydroxybenzotriazole hydrate (8.61 g, 63.7 mmol) were dissolved in N,N-dimethylformamide (50 ml) and dichloromethane (200 ml). The solution was cooled to 0° C. N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (8.67 g, 63.7 mmol) was added. The reaction mixture was stirred for 30 min at 0° C. A 8.0 M solution of methyl amine (39 ml, 318 mmol) was added. The reaction mixture was stirred for 16 h, while it was slowly warming up to room temperature. It was diluted with ethyl acetate (600 ml) and washed with a 10% aqueous solution of sodium hydrogen sulfate (2×300 ml). The combined aqueous phases were extracted with ethyl acetate. The combined organic layers were washed with saturated sodium hydrogen carbonate solution (300 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (180 g), using ethyl acetate/heptane (1:1) as eluent to give 4.90 g of 2-(2-hydroxyphenyl)-N-methylacetamide. The reaction mixture was stirred for 16 h, while it was slowly warming up to room temperature washed with a 10% aqueous solution of sodium hydrogen sulfate (2×300 ml) The combined aqueous phases were extracted with ethyl acetate The combined organic layers were washed with saturated sodium hydrogen carbonate solution (300 ml) dried over magnesium sulfate The solvent was removed in vacuo The crude product was purified by flash chromatography on silica (180 g)

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

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

Procedure: Potassium carbonate (2.81 g, 20.34 mmol) was given to a solution of 2-(2-hydroxyphenyl)-N-methylacetamide (3.36 g, 20.34 mmol) in acetone (150 ml). Ethyl bromoacetate (2.13 ml, 19.32 mmol) and potassium iodide (166 mg, 1.02 mmol) were added successively. The reaction mixture was heated to reflux for 6 h. It was left at room temperature for 16 h. The solid was filtered off. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (80 g), using ethyl acetate/dichloromethane (1:1) as eluent, to give 5.00 g of ethyl 2-(2-((N-methylcarbamoyl)methyl)phenoxy)acetate. The reaction mixture was heated to reflux for 6 h The solid was filtered off The solvent was removed in vacuo The crude product was purified by flash chromatography on silica (80 g)

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

Procedure: (2-Hydroxyphenyl)acetic acid (9.89 g, 63.7 mmol) and 1hydroxybenzotriazole hydrate (8.61 g, 63.7 mmol) were dissolved in N,N-dimethylformamide (50 ml) and dichloromethane (200 ml). The solution was cooled to 0° C. N-(3-Dimethylaminopropyl)-N -ethylcarbodiimide hydrochloride (8.67 g, 63.7 mmol) was added. The reaction mixture was stirred for 30 min at 0° C. A 8.0 M solution of methyl amine (39 ml, 318 mmol) was added. The reaction mixture was stirred for 16 h, while it was slowly warming up to room temperature. It was diluted with ethyl acetate (600 ml) and washed with a 10% aqueous solution of sodium hydrogen sulfate (2×300 ml). The combined aqueous phases were extracted with ethyl acetate. The combined organic layers were washed with saturated sodium hydrogen carbonate solution (300 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (180 g), using ethyl acetate/heptane(1:1) as eluent to give 4.90 g of 2-(2-hydroxyphenyl)-N-methylacetamide. The reaction mixture was stirred for 16 h, while it was slowly warming up to room temperature washed with a 10% aqueous solution of sodium hydrogen sulfate (2×300 ml) The combined aqueous phases were extracted with ethyl acetate The combined organic layers were washed with saturated sodium hydrogen carbonate solution (300 ml) dried over magnesium sulfate The solvent was removed in vacuo The crude product was purified by flash chromatography on silica (180 g)

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

Procedure: (2-Hydroxyphenyl)acetic acid (9.89 g, 63.7 mmol) and 1hydroxybenzotriazole hydrate (8.61 g, 63.7 mmol) were dissolved in N,N-dimethylformamide (50 ml) and dichloromethane (200 ml). The solution was cooled to 0° C. N-(3-Dimethylaminopropyl)-N -ethylcarbodiimide hydrochloride (8.67 g, 63.7 mmol) was added. The reaction mixture was stirred for 30 min at 0° C. A 8.0 M solution of methyl amine (39 ml, 318 mmol) was added. The reaction mixture was stirred for 16 h, while it was slowly warming up to room temperature. It was diluted with ethyl acetate (600 ml) and washed with a 10% aqueous solution of sodium hydrogen sulfate (2×300 ml). The combined aqueous phases were extracted with ethyl acetate. The combined organic layers were washed with saturated sodium hydrogen carbonate solution (300 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (180 g), using ethyl acetate/heptane(1:1) as eluent to give 4.90 g of 2-(2-hydroxyphenyl)-N-methylacetamide. The reaction mixture was stirred for 16 h, while it was slowly warming up to room temperature washed with a 10% aqueous solution of sodium hydrogen sulfate (2×300 ml) The combined aqueous phases were extracted with ethyl acetate The combined organic layers were washed with saturated sodium hydrogen carbonate solution (300 ml) dried over magnesium sulfate The solvent was removed in vacuo The crude product was purified by flash chromatography on silica (180 g)

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

Procedure: (2R)-2-(N-((2E)-5-Amino-5-methylhex-2-enoyl)-N-methylamino)-N-(2-(2-(2-hydroxyethoxy)phenyl)ethyl)-N-methyl-3-(2-naphthyl)propionamide ##STR130## 2-(2-Hydroxyphenyl)-N-methylacetamide ##STR131## (2-Hydroxyphenyl)acetic acid (9.89 g, 63.7 mmol) and 1-hydroxybenzotriazole hydrate (8.61 g, 63.7 mmol) were dissolved in N,N-dimethylformamide (50 ml) and dichloromethane (200 ml). The solution was cooled to 0° C. N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (8.67 g, 63.7 mmol) was added. The reaction mixture was stirred for 30 min at 0° C. A 8.0M solution of methyl amine (39 ml, 318 mmol) was added. The reaction mixture was stirred for 16 h, while it was slowly warming up to room temperature. It was diluted with ethyl acetate (600 ml) and washed with a 10% aqueous solution of sodium hydrogen sulfate (2×300 ml). The combined aqueous phases were extracted with ethyl acetate. The combined organic layers were washed with saturated sodium hydrogen carbonate solution (300 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (180 g), using ethyl acetate/heptane (1:1) as eluent to give 4.90 g of 2-(2-hydroxyphenyl)-N-methylacetamide. The reaction mixture was stirred for 16 h, while it was slowly warming up to room temperature washed with a 10% aqueous solution of sodium hydrogen sulfate (2×300 ml) The combined aqueous phases were extracted with ethyl acetate The combined organic layers were washed with saturated sodium hydrogen carbonate solution (300 ml) dried over magnesium sulfate The solvent was removed in vacuo The crude product was purified by flash chromatography on silica (180 g)

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

Procedure: Potassium carbonate (2.81 g, 20.34 mmol) was given to a solution of 2-(2-hydroxyphenyl)-N-methylacetamide (3.36 g, 20.34 mmol) in acetone (150 ml). Ethyl bromoacetate (2.13 ml, 19.32 mmol) and potassium iodide (166 mg, 1.02 mmol) were added successively. The reaction mixture was heated to reflux for 6 h. It was left at room temperature for 16 h. The solid was filtered off. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (80 g), using ethyl acetate/dichloromethane (1:1) as eluent, to give 5.00 g of ethyl 2-(2-((N-methylcarbamoyl)methyl)phenoxy)acetate. The reaction mixture was heated to reflux for 6 h The solid was filtered off The solvent was removed in vacuo The crude product was purified by flash chromatography on silica (80 g)

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

Procedure: (2-Hydroxyphenyl)acetic acid (9.89 g, 63.7 mmol) and 1-hydroxybenzotriazole hydrate (8.61 g, 63.7 mmol) were dissolved in N,N-dimethylformamide (50 ml) and dichloromethane (200 ml). The solution was cooled to 0° C. N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (8.67 g, 63.7 mmol) was added. The reaction mixture was stirred for 30 min at 0° C. A 8.0 M solution of methyl amine (39 ml, 318 mmol) was added. The reaction mixture was stirred for 16 h, while it was slowly warming up to room temperature. It was diluted with ethyl acetate (600 ml) and washed with a 10% aqueous solution of sodium hydrogen sulfate (2×300 ml). The combined aqueous phases were extracted with ethyl acetate. The combined organic layers were washed with saturated sodium hydrogen carbonate solution (300 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (180 g), using ethyl acetate/heptane (1:1) as eluent to give 4.90 g of 2-(2-hydroxyphenyl)-N-methylacetamide. The reaction mixture was stirred for 16 h, while it was slowly warming up to room temperature washed with a 10% aqueous solution of sodium hydrogen sulfate (2×300 ml) The combined aqueous phases were extracted with ethyl acetate The combined organic layers were washed with saturated sodium hydrogen carbonate solution (300 ml) dried over magnesium sulfate The solvent was removed in vacuo The crude product was purified by flash chromatography on silica (180 g)

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

Procedure: A mixture of 2-(2-hydroxyphenyl)-N-methylacetamide (1.00 g, 6.1 mmol) prepared according to a known procedure (Bernd, Peschke, Eur. J. Med. Chem., 2000, 35, 599-618), (2S)-oxiran-2-ylmethyl 3-nitrobenzenesulfonate (1.58 g, 6.1 mmol) and cesium carbonate (2.37 g, 7.3 mmol) in 1-methylpyrrolidin-2-one (15 ml) was stirred at room temperature overnight. The mixture was diluted with water and extracted with ethyl acetate, the combined organic layers were dried with sodium sulphate, volatiles were removed in vacuo. The residue was purified by recrystillaziation from ethyl acetate/heptane; (390 mg) of the subtitle compound was obtained. prepared extracted with ethyl acetate the combined organic layers were dried with sodium sulphate, volatiles were removed in vacuo The residue was purified by recrystillaziation from ethyl acetate/heptane

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

Procedure: Potassium carbonate (2.81 g, 20.34 mmol) was given to a solution of 2-(2-hydroxyphenyl)-N-methylacetamide (3.36 g, 20.34 mmol) in acetone (150 ml). Ethyl bromoacetate (2.13 ml, 19.32 mmol) and potassium iodide (166 mg, 1.02 mmol) were added successively. The reaction mixture was heated to reflux for 6 h. It was left at room temperature for 16 h. The solid was filtered off. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (80 g), using ethyl acetate/dichloromethane (1:1) as eluent, to give 5.00 g of ethyl 2-(2-((N-methylcarbamoyl)methyl)phenoxy)acetate. The reaction mixture was heated to reflux for 6 h The solid was filtered off The solvent was removed in vacuo The crude product was purified by flash chromatography on silica (80 g)