N-(2-fluoro-4-hydroxyphenyl)acetamide

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:; See reaction.notes.procedure_details.

実験手順: 5.0- Grams of 3-fluoro-4-nitrophenol, 3.57 g of acetic anhydride, 0.72 g of platinum dioxide and 50 ml of ethyl acetate were added to a reactor, and the atmosphere in the reactor was replaced by a hydrogen stream with stirring. Stirring was then continued at room temperature for 6 hours while introducing a hydrogen gas. Thereafter, the reaction solution was filtered off, and the filtrate was washed with two 50-ml portions of a 5% aqueous sodium hydrogencarbonate solution, dried and concentrated. The residue was subjected to chromatography on silica gel to obtain 4.47 g of 4-acetylamino-3fluorophenol. Stirring Thereafter, the reaction solution was filtered off the filtrate was washed with two 50-ml portions of a 5% aqueous sodium hydrogencarbonate solution dried concentrated

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

実験手順: 0.93 Gram of 4-acetylamino-3-fluorophenol, 0.15 g of potassium carbonate and 15 ml of dimethylformamide were added to a reactor and stirred for 20 minutes at an oil bath temperature of from 60° to 70° C. Thereafter, this solution was violently stirred at the same temperature for 1 hour under the stream of a tetrafluoroethylene gas in excess of said phenol. The reaction solution was cooled and after adding water, extracted with two 100-ml portions of diethyl ether. The ether layers were combined, washed with water, dried and concentrated to obtain a crude product. This crude product was subjected to chromatography on silica gel to obtain 1.46 g of 4-acetylamino-3-fluoro-1-(1,1,2,2-tetrafluoroethoxy)benzene. The reaction solution was cooled extracted with two 100-ml portions of diethyl ether washed with water dried concentrated to obtain a crude product

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

実験手順: 5.0 Grams of 3-fluoro-4-nitrophenol, 3.57 g of acetic anhydride, 0.72 g of platinum dioxide and 50 ml of ethyl acetate were added to a reactor, and the atmosphere in the reactor was replaced by a hydrogen stream with stirring. Stirring was then continued at room temperature for 6 hours while introducing a hydrogen gas. Thereafter, the reaction solution was filtered off, and the filtrate was washed with two 50-ml portions of a 5% aqueous sodium hydrogencarbonate solution, dried and concentrated. The residue was subjected to chromatography on silica gel to obtain 4.47 g of 4-acetylamino-3-fluorophenol. Stirring Thereafter, the reaction solution was filtered off the filtrate was washed with two 50-ml portions of a 5% aqueous sodium hydrogencarbonate solution dried concentrated

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

実験手順: 5.0 Grams of 3-fluoro-4-nitrophenol, 3.57 g of acetic anhydride, 0.72 g of platinum dioxide and 50 ml of ethyl acetate were added to a reactor, and the atmosphere in the reactor was replaced by a hydrogen stream with stirring. Stirring was then continued at room temperature for 6 hours while introducing a hydrogen gas. Thereafter, the reaction solution was filtered off, and the filtrate was washed with two 50-ml portions of a 5% aqueous sodium hydrogencarbonate solution, dried and concentrated. The residue was subjected to chromatography on silica gel to obtain 4.47 g of 4-acetylamino-3-fluorophenol. Stirring Thereafter, the reaction solution was filtered off the filtrate was washed with two 50-ml portions of a 5% aqueous sodium hydrogencarbonate solution dried concentrated

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

実験手順: 3-(4-Acetylamino-3-fluorophenoxy)-N-(4-cyano-3-methylphenyl)-2-hydroxy-2-methylpropionamide was prepared as described in Example 1 starting from N-(2-fluoro-4-hydroxyphenyl)acetamide and 2-methyl-oxirane-2-carboxylic acid (4-cyano-3-methylphenyl)amide. 1H NMR (DMSO-d6): 1.41 (3H, s), 2.02 (3H, s), 2.44 (3H, s), 3.95 (1H, d, J=9.8 Hz), 4.26 (1H, d, J=9.8 Hz), 6.21 (1H, bs), 6.72 (1H, m), 6.86 (1H, m),7.56 (1H, m,) 7.69 (1H, d, J=9.0 Hz), 7.78 (1H, dd, J=9.0 Hz and 2.2 Hz), 7.93 (1H, d, J=2.2 Hz), 9.51 (1H, s), 9.99 (1H, bs).

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

実験手順: (2S)-3-(4-Acetylamino-3-fluorophenoxy)-2-hydroxy-2-methyl-N-(3-methyl-4-nitrophenyl)propionamide was prepared according to the method B as described in Example 3e starting from 4-acetylamino-3-fluorophenol and N-[3-methyl-4-(nitro)phenyl]-(2R)-3-bromo-2-hydroxy-2-methylpropanamide. 1H NMR (DMSO-d6): 1.42 (3H, s), 2.02 (3H, s), 2.53 (3H, s), 3.97 (1H, d, J=9.7 Hz), 4.21 (1H, d, J=9.7 Hz), 6.23 (1H, bs), 6.72 (1H, m), 6.90 (1H, m), 7.56 (1H, m), 7.88 (1H, dd, J=9.0 Hz and 2.2 Hz), 7.93 (1H, d, J=2.2 Hz), 8.03 (1H, d, J=9.0 Hz), 9.51 (1H, s), 10.15 (1H, bs).

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

実験手順: The compound was synthesised according to the procedure described in Example 1c. N-(2-Fluoro-4-hydroxyphenyl)acetamide (0.5 g, 3.0 mmol) and 2-methyloxirane-2-carboxylic acid (3-methyl-4-nitrophenyl)amide (0.6 g, 2.5 mmol) was used as starting materials. The product was crystallised from the mixture of ethyl acetate and diethyl ether (1:1). The yield was 0.39 g. 1H NMR (DMSO-d6): 1.42 (3H, s), 2.02 (3H, s), 2.53 (3H, s), 3.97 (1H, d, J=9.7 Hz), 4.21 (1H, d, J=9.7 Hz), 6.23 (1H, bs), 6.72 (1H, m), 6.90 (1H, m), 7.56 (1H, m), 7.88 (1H, dd, J=9.0 Hz and 2.2 Hz), 7.93 (1H, d, J=2.2 Hz), 8.03 (1H, d, J=9.0 Hz), 9.51 (1H, s), 10.15 (1H, bs). The compound was synthesised The product was crystallised from the mixture of ethyl acetate and diethyl ether (1:1)

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

実験手順: Acetic anhydride (1.3 ml, 13.8 mmol) was added dropwise to a solution of 4-amino-3-fluorophenol (1.0 g, 7.9 mmol) in acetic acid (25 ml) at room temperature. The reaction mixture was stirred at room temperature for 2 h and water (2 ml) was added and the stirring was continued for 30 minutes at room temperature. The mixture was evaporated to dryness in vacuo. The yield of the crude product was 1.3 g (100%) and it was used without further purification. the stirring was continued for 30 minutes at room temperature The mixture was evaporated to dryness in vacuo was used without further purification

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

実験手順: 3-(4-Acetylamino-3-fluorophenoxy)-N-(4-cyano-3-methylphenyl)-2-hydroxy-2-methylpropionamide was prepared as described in Example 1 starting from N-(2-fluoro-4-hydroxyphenyl)acetamide and 2-methyl-oxirane-2-carboxylic acid (4-cyano-3-methylphenyl)amide. 1H NMR (DMSO-d6): 1.41 (3H, s), 2.02 (3H, s), 2.44 (3H, s), 3.95 (1H, d, J=9.8 Hz), 4.26 (1H, d, J=9.8 Hz), 6.21 (1H, bs), 6.72 (1H, m), 6.86 (1H, m),7.56 (1H, m,) 7.69 (1H, d, J=9.0 Hz), 7.78 (1H, dd, J=9.0 Hz and 2.2 Hz), 7.93 (1H, d, J=2.2 Hz), 9.51 (1H, s), 9.99 (1H, bs).

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

実験手順: (2S)-3-(4-Acetylamino-3-fluorophenoxy)-2-hydroxy-2-methyl-N-(3-methyl-4-nitrophenyl)propionamide was prepared according to the method B as described in Example 3e starting from 4-acetylamino-3-fluorophenol and N-[3-methyl-4-(nitro)phenyl]-(2R)-3-bromo-2-hydroxy-2-methylpropanamide. 1H NMR (DMSO-d6): 1.42 (3H, s), 2.02 (3H, s), 2.53 (3H, s), 3.97 (1H, d, J=9.7 Hz), 4.21 (1H, d, J=9.7 Hz), 6.23 (1H, bs), 6.72 (1H, m), 6.90 (1H, m), 7.56 (1H, m), 7.88 (1H, dd, J=9.0 Hz and 2.2 Hz), 7.93 (1H, d, J=2.2 Hz), 8.03 (1H, d, J=9.0 Hz), 9.51 (1H, s), 10.15 (1H, bs).