4'-Fluoro-2-phenylacetophenone

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: A mixture of 1-(4-fluorophenyl)-2-phenylethanone (200 mg, 0.93 mmol), 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (164 mg, 0.78 mmol), urea (140 mg, 2.3 mmol), and concentrated HCl solution (0.08 mL, 0.93 mmol) in EtOH (5 mL) was refluxed overnight. The mixture was evaporated in vacuo, and the residue was purified by preparative HPLC to give Compound 35 (120 mg, yield 29%). 1H NMR (DMSO-d6 300 MHz): δ 10.28 (s, 1H), 8.76 (s, 1H), 7.54 (s, 1H), 7.42 (s, 1H), 7.25-7.21 (m, 2H), 7.16 (s, 1H), 7.11-6.97 (m, 5H), 6.81 (d, J=7.5 Hz, 2H), 5.19 (s, 1H), 4.08-3.99 (m, 2H), 1.32 (t, J=6.6 Hz, 3H); MS (ESI): m/z 450.0 [M+1]+. was refluxed overnight The mixture was evaporated in vacuo the residue was purified by preparative HPLC

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: A mixture of 1-(4-fluorophenyl)-2-phenylethanone (200 mg, 0.93 mmol), 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (164 mg, 0.78 mmol), urea (140 mg, 2.3 mmol), and concentrated HCl solution (0.08 mL, 0.93 mmol) in EtOH (5 mL) was refluxed overnight. The mixture was evaporated in vacuo, and the residue was purified by preparative HPLC to give Compound 35 (120 mg, yield 29%). 1H NMR (DMSO-d6 300 MHz): δ 10.28 (s, 1H), 8.76 (s, 1H), 7.54 (s, 1H), 7.42 (s, 1H), 7.25-7.21 (m, 2H), 7.16 (s, 1H), 7.11-6.97 (m, 5H), 6.81 (d, J=7.5 Hz, 2H), 5.19 (s, 1H), 4.08-3.99 (m, 2H), 1.32 (t, J=6.6 Hz, 3H); MS (ESI): m/z 450.0 [M+1]+. was refluxed overnight The mixture was evaporated in vacuo the residue was purified by preparative HPLC

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

実験手順: A mixture of 1-(4-fluorophenyl)-2-phenylethanone (200 mg, 0.93 mmol), 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (164 mg, 0.78 mmol), urea (140 mg, 2.3 mmol), and concentrated HCl solution (0.08 mL, 0.93 mmol) in EtOH (5 mL) was refluxed overnight. The mixture was evaporated in vacuo, and the residue was purified by preparative HPLC to give Compound 35 (120 mg, yield 29%). 1H NMR (DMSO-d6 300 MHz): δ 10.28 (s, 1H), 8.76 (s, 1H), 7.54 (s, 1H), 7.42 (s, 1H), 7.25-7.21 (m, 2H), 7.16 (s, 1H), 7.11-6.97 (m, 5H), 6.81 (d, J=7.5 Hz, 2H), 5.19 (s, 1H), 4.08-3.99 (m, 2H), 1.32 (t, J=6.6 Hz, 3H); MS (ESI): m/z 450.0 [M+1]+. was refluxed overnight The mixture was evaporated in vacuo the residue was purified by preparative HPLC

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

実験手順: A mixture of 1-(4-fluorophenyl)-2-phenylethanone (200 mg, 0.93 mmol), 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (164 mg, 0.78 mmol), urea (140 mg, 2.3 mmol), and concentrated HCl solution (0.08 mL, 0.93 mmol) in EtOH (5 mL) was refluxed overnight. The mixture was evaporated in vacuo, and the residue was purified by preparative HPLC to give Compound 35 (120 mg, yield 29%). 1H NMR (DMSO-d6 300 MHz): δ 10.28 (s, 1H), 8.76 (s, 1H), 7.54 (s, 1H), 7.42 (s, 1H), 7.25-7.21 (m, 2H), 7.16 (s, 1H), 7.11-6.97 (m, 5H), 6.81 (d, J=7.5 Hz, 2H), 5.19 (s, 1H), 4.08-3.99 (m, 2H), 1.32 (t, J=6.6 Hz, 3H); MS (ESI): m/z 450.0 [M+1]+. was refluxed overnight The mixture was evaporated in vacuo the residue was purified by preparative HPLC

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

実験手順: A mixture of 1-(4-fluorophenyl)-2-phenylethanone (200 mg, 0.93 mmol), 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (164 mg, 0.78 mmol), urea (140 mg, 2.3 mmol), and concentrated HCl solution (0.08 mL, 0.93 mmol) in EtOH (5 mL) was refluxed overnight. The mixture was evaporated in vacuo, and the residue was purified by preparative HPLC to give Compound 35 (120 mg, yield 29%). 1H NMR (DMSO-d6 300 MHz): δ 10.28 (s, 1H), 8.76 (s, 1H), 7.54 (s, 1H), 7.42 (s, 1H), 7.25-7.21 (m, 2H), 7.16 (s, 1H), 7.11-6.97 (m, 5H), 6.81 (d, J=7.5 Hz, 2H), 5.19 (s, 1H), 4.08-3.99 (m, 2H), 1.32 (t, J=6.6 Hz, 3H); MS (ESI): m/z 450.0 [M+1]+. was refluxed overnight The mixture was evaporated in vacuo the residue was purified by preparative HPLC

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

実験手順: A mixture of 1-(4-fluorophenyl)-2-phenylethanone (200 mg, 0.93 mmol), 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (164 mg, 0.78 mmol), urea (140 mg, 2.3 mmol), and concentrated HCl solution (0.08 mL, 0.93 mmol) in EtOH (5 mL) was refluxed overnight. The mixture was evaporated in vacuo, and the residue was purified by preparative HPLC to give Compound 35 (120 mg, yield 29%). 1H NMR (DMSO-d6 300 MHz): δ 10.28 (s, 1H), 8.76 (s, 1H), 7.54 (s, 1H), 7.42 (s, 1H), 7.25-7.21 (m, 2H), 7.16 (s, 1H), 7.11-6.97 (m, 5H), 6.81 (d, J=7.5 Hz, 2H), 5.19 (s, 1H), 4.08-3.99 (m, 2H), 1.32 (t, J=6.6 Hz, 3H); MS (ESI): m/z 450.0 [M+1]+. was refluxed overnight The mixture was evaporated in vacuo the residue was purified by preparative HPLC

反応条件: temp:12.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sulfuryl chloride (66.6 g, 0.493 mol) is taken in a 4 necked RB flask equipped with mechanical strring rod, pressure equalization funnel and a CaCl2 guard tube. The contents of the flask are cooled to 10-15° C. A solution of 1-(4-Fluorophenyl)-2-phenyl ethanone (100 g, 0.467 mol) in 150 ml of methylene chloride is added to the above flask in about 30-45 min while maintaining the temperature between 10-15° C. After completion of addition, the reaction mass is then stirred for additional 2½ hours at 15-20° C. TLC examination of reaction mixture showed the absence of starting material. The reaction mixture is slowly poured over crushed ice (600 g) and further dilueted with methylene chloride (200 ml). The methylene chloride layer is separated and washed twice with 5% aqueous sodium bicarbonate (200 ml) followed by 5% aqueous sodium chloride(200 ml). The methylene chloride layer is dried over sodium sulphate. Methylene chloride is removed by distillation completely to obtain 2-Chloro-1-(4-fluorophenyl)-2-phenylethanone as a pale yellow liquid. equipped with mechanical strring rod, pressure equalization funnel and a CaCl2 guard tube while maintaining the temperature between 10-15° C After completion of addition TLC examination of reaction mixture The reaction mixture is slowly poured The methylene chloride layer is separated washed twice with 5% aqueous sodium bicarbonate (200 ml) The methylene chloride layer is dried over sodium sulphate Methylene chloride is removed by distillation completely

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

実験手順: Fluorobenzene (100 g, 1.04 mol) is taken in a clean and dry 4 necked RB flask equipped with mechanical stirring rod, pressure equalization funnel, N2 inlet and a CaCl2 guard tube. The contents of the flask are cooled to 0° C. in an ice bath under a stream of N2 gas. 103 g (1.54 mol) of powdered aluminum chloride are added into the flask under stirring. The contents of the flask are further cooled to −10° C. by adding common salt to ice bath. Phenyl acetyl chloride (110.75 g, 1.43 mol) is placed in the pressure equalization funnel fitted to the flask and added drop wise manner in 2-2½ hours, while maintaining the temperature of the reaction between −10° to 0° C. After the addition the reaction is maintained for a further period of 2 hours between −10° to 0° C. In process sample of reaction mixture showed the area % of 1-(4-Fluorophenyl)-2-phenyl ethanone by HPLC as 99.02% and deoxy benzoin content as nil. The reaction mixture is then poured slowly into a mixture of ice (300 g), water (300 ml) and Conc.hydrochloric acid (30 ml) while maintain the temperature between −10 to 5° C. the contents are stirred for ½ hr at this temperature. The solid thus obtained is dissolved in methylene chloride (1.0 L) and separated the organic phase. The aqueous phase is extracted with methylene chloride (500 ml).The combined methylene chloride extract is sequentially washed with 5% aqueous sodium bicarbonate (600 ml), water (600 ml) and 5% sodium chloride (400 ml). The methylene chloride extract is then transferred into a 4 necked RB flask equipped with mechanical strring rod, pressure equalization funnel and a CaCl2 guard tube. 4 ml of a 30% hydrobromic acid in acetic acid is then added, followed by gradual addition of a cold solution of bromine 109 g, 0.68 mole) in 200 ml of methylene chloride at 26±2° C. Bromine solution is added in such a manner that it is consumed instantly as indicated by colouration of reaction mixture. After addition of bromine solution the reaction mixture is cooled to 19±1° C., treated with 5% aqueous sodium sulphite (400 ml) and stirred for about lhr at 21.5±3.5° C. The organic layer is then separated and is subjected to the above operation twice with 5% aqueous sodium sulphite (2×400 ml). The organic layer is stirred with 5% aqueous sodium bicarbonate (400 ml) for about 1 hr at 21.5±3.5° C. and separated. The organic layer is finally stirred with 5% aqueous sodium chloride(400 ml) and separated. The organic layer is dried over sodium sulphate and filtered. Methylene chloride is removed by distillation and the syrup thus obtained solidified on standing in to a pale orange coloured solid. Yield 183 g (85.9%) dry 4 necked RB flask equipped with mechanical stirring rod, pressure equalization funnel, N2 inlet and a CaCl2 guard tube The contents of the flask are further cooled to −10° C. by adding common salt to ice bath fitted to the flask added drop wise manner in 2-2½ hours while maintaining the temperature of the reaction between −10° to 0° C After the addition the reaction is maintained for a further period of 2 hours between −10° to 0° C In process sample of reaction mixture are stirred for ½ hr at this temperature The solid thus obtained separated the organic phase The aqueous phase is extracted with methylene chloride (500 ml).The combined methylene chloride extract is sequentially washed with 5% aqueous sodium bicarbonate (600 ml), water (600 ml) and 5% sodium chloride (400 ml) The methylene chloride extract equipped with mechanical strring rod, pressure equalization funnel and a CaCl2 guard tube 4 ml of a 30% hydrobromic acid in acetic acid is then added is consumed instantly as indicated by colouration of reaction mixture is cooled to 19±1° C. stirred for about lhr at 21.5±3.5° C The organic layer is then separated The organic layer is stirred with 5% aqueous sodium bicarbonate (400 ml) for about 1 hr at 21.5±3.5° C. separated The organic layer is finally stirred with 5% aqueous sodium chloride(400 ml) separated The organic layer is dried over sodium sulphate filtered Methylene chloride is removed by distillation the syrup thus obtained

反応条件: temp:19.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Methylene chloride (1 L) is taken in a 4 necked RB flask equipped with mechanical strring rod, pressure equalization funnel and a CaCl2 guard tube. 100 g (0.466 mol) of 1-(4-Fluorophenyl)-2-phenyl ethanone is introduced in to the above flask and stirred for 5 minutes to obtain a clear solution.2 ml of a 30% hydrobromic acid in acetic acid is then added, followed by gradual addition of a cold solution of bromine (73 g, 0.456 mole) in 200 ml of methylene chloride at 26±2° C. Bromine solution is added in such a manner that it is consumed instantly as indicated by colouration of reaction mixture. After addition of bromine solution the reaction mixture is cooled to 19±1° C., treated with 5% aqueous sodium sulphite (200 ml) and stirred for about lhr at 21.5±3.5° C. The organic layer is then separated and is subjected to the above operation twice with 5% aqueous sodium sulphite (2×200 ml). The organic layer is then stirred with 5% aqueous sodium bicarbonate (200 ml) for about 1 hr at 21.5±3.5° C. and separated. The organic layer is finally stirred with 5% aqueous sodium chloride(200 ml) and separated. The organic layer is dried over sodium sulphate and filtered. Methylene chloride is removed by distillation and the syrup thus obtained solidified on standing in to a pale orange coloured solid. Yield 129 g (94.8%) equipped with mechanical strring rod, pressure equalization funnel and a CaCl2 guard tube to obtain a clear solution is consumed instantly as indicated by colouration of reaction mixture stirred for about lhr at 21.5±3.5° C The organic layer is then separated The organic layer is then stirred with 5% aqueous sodium bicarbonate (200 ml) for about 1 hr at 21.5±3.5° C. separated The organic layer is finally stirred with 5% aqueous sodium chloride(200 ml) separated The organic layer is dried over sodium sulphate filtered Methylene chloride is removed by distillation the syrup thus obtained

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

実験手順: 28.4 g of phenylacetyl chloride was dissolved in 130 ml of fluorobenzene and cooled in ice. This solution was added to 27.0 g of freshly powdered aluminum chloride with continued cooling and stirring. After the vigorous reaction subsided, the mixture was stirred at room temperature overnight and then poured onto 150 g of ice containing 50 ml of concentrated hydrochloric acid. Extraction gave a pale brown solid. Recrystallization from petroleum ether gave 4-fluorodeoxybenzoin, 2A, as a white solid, mp: 80°-81° C. cooled in ice with continued cooling After the vigorous reaction the mixture was stirred at room temperature overnight Extraction gave a pale brown solid Recrystallization from petroleum ether