4-(2-bromoethyl)-3-chloro-1,3-dihydroindol-2-one

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: 4-(2'-Bromoethyl)-3-chloro-1,3-dihydro-2H-indol-2-one (23.6 g. 86 mmol), sodium hypophosphite hydrate (35 g) and 10% palladium/carbon (60% w/w wet, 2.6 g) were stirred in industrial methylated spirit (250 ml)/water (30 ml) at 80° C. The reaction was complete after 2 hours as monitored by HPLC. Inorganic components were removed by filtration and the organic solvent was removed in vaccuo. The solid residue was slurried in water (100 ml) and dried overnight to give 17.0 g (82%) of 4-(2'-bromoethyl)-1,3-dihydro-2H-indol-2-one. Inorganic components were removed by filtration the organic solvent was removed in vaccuo dried overnight

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a precooled solution of ferric chloride (28.5 kg) in dichloromethane (340 1) at 0° C. was added acetyl chloride (9.2 kg) at such a rate that the reaction temperature did not exceed 5° C. The reaction mixture was stirred at between 0° and 5° C. for 15 minutes. To the mixture was added a pre-dryed solution of 2-(2'-bromoethyl)-β-nitrostyrene [12.88 kg (16.22 kg wet:water content 20.6%)]in dichloromethane (55 litres) at such a rate that the reaction temperature did not exceed 5° C. The reaction mixture was stirred for 5 hours at a temperature between 5 and 10° C. Analysis by TLC confirmed that the reaction had gone to completion. Water (240 1) was then added to the reaction mixture at such a rate so that the temperature did not exceed 20° C. The mixture was then stirred for 30 minutes. The dichloromethane layer was isolated and washed a further three times with water (three times 120 1). The dichloromethane layer was then distilled to a volume of about 60 1. After cooling to 20° C. petroleum ether (60/80 grade. 40 1) was added and the resulting precipitate was stirred at 10° C. for 30 minutes. HPLC analysis of the crude reaction mixture indicated a purity of 93.22% of the required product. 4-(2'-bromo-ethyl)-3-chloro-1,3-dihydro-2H-indol-2-on by filtration, the filtrate washed with petroleum ether (60 1) and dried at 80° C. overnight to give 10.8 kg (78%) of of the title compound. did not exceed 5° C did not exceed 5° C The reaction mixture was stirred for 5 hours at a temperature between 5 and 10° C did not exceed 20° C The mixture was then stirred for 30 minutes washed a further three times with water (three times 120 1) The dichloromethane layer was then distilled to a volume of about 60 1 was added the resulting precipitate was stirred at 10° C. for 30 minutes HPLC analysis of the crude reaction mixture

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: 4-(2'-Bromoethyl)-3-chloro-1,3-dihydro-2H-indol-2-one (23.6 g. 86 mmol), sodium hypophosphite hydrate (35 g) and 10% palladium/carbon (60% w/w wet, 2.6 g) were stirred in industrial methylated spirit (250 ml)/water (30 ml) at 80° C. The reaction was complete after 2 hours as monitored by HPLC. Inorganic components were removed by filtration and the organic solvent was removed in vaccuo. The solid residue was slurried in water (100 ml) and dried overnight to give 17.0 g (82%) of 4-(2'-bromoethyl)-1,3-dihydro-2H-indol-2-one. Inorganic components were removed by filtration the organic solvent was removed in vaccuo dried overnight

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a precooled solution of ferric chloride (28.5 kg) in dichloromethane (340 1) at 0° C. was added acetyl chloride (9.2 kg) at such a rate that the reaction temperature did not exceed 5° C. The reaction mixture was stirred at between 0° and 5° C. for 15 minutes. To the mixture was added a pre-dryed solution of 2-(2'-bromoethyl)-β-nitrostyrene [12.88 kg (16.22 kg wet:water content 20.6%)]in dichloromethane (55 litres) at such a rate that the reaction temperature did not exceed 5° C. The reaction mixture was stirred for 5 hours at a temperature between 5 and 10° C. Analysis by TLC confirmed that the reaction had gone to completion. Water (240 1) was then added to the reaction mixture at such a rate so that the temperature did not exceed 20° C. The mixture was then stirred for 30 minutes. The dichloromethane layer was isolated and washed a further three times with water (three times 120 1). The dichloromethane layer was then distilled to a volume of about 60 1. After cooling to 20° C. petroleum ether (60/80 grade. 40 1) was added and the resulting precipitate was stirred at 10° C. for 30 minutes. HPLC analysis of the crude reaction mixture indicated a purity of 93.22% of the required product. 4-(2'-bromo-ethyl)-3-chloro-1,3-dihydro-2H-indol-2-on by filtration, the filtrate washed with petroleum ether (60 1) and dried at 80° C. overnight to give 10.8 kg (78%) of of the title compound. did not exceed 5° C did not exceed 5° C The reaction mixture was stirred for 5 hours at a temperature between 5 and 10° C did not exceed 20° C The mixture was then stirred for 30 minutes washed a further three times with water (three times 120 1) The dichloromethane layer was then distilled to a volume of about 60 1 was added the resulting precipitate was stirred at 10° C. for 30 minutes HPLC analysis of the crude reaction mixture

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a precooled solution of ferric chloride (28.5 kg) in dichloromethane (340 1) at 0° C. was added acetyl chloride (9.2 kg) at such a rate that the reaction temperature did not exceed 5° C. The reaction mixture was stirred at between 0° and 5° C. for 15 minutes. To the mixture was added a pre-dryed solution of 2-(2'-bromoethyl)-β-nitrostyrene [12.88 kg (16.22 kg wet:water content 20.6%)]in dichloromethane (55 litres) at such a rate that the reaction temperature did not exceed 5° C. The reaction mixture was stirred for 5 hours at a temperature between 5 and 10° C. Analysis by TLC confirmed that the reaction had gone to completion. Water (240 1) was then added to the reaction mixture at such a rate so that the temperature did not exceed 20° C. The mixture was then stirred for 30 minutes. The dichloromethane layer was isolated and washed a further three times with water (three times 120 1). The dichloromethane layer was then distilled to a volume of about 60 1. After cooling to 20° C. petroleum ether (60/80 grade. 40 1) was added and the resulting precipitate was stirred at 10° C. for 30 minutes. HPLC analysis of the crude reaction mixture indicated a purity of 93.22% of the required product. 4-(2'-bromo-ethyl)-3-chloro-1,3-dihydro-2H-indol-2-on by filtration, the filtrate washed with petroleum ether (60 1) and dried at 80° C. overnight to give 10.8 kg (78%) of of the title compound. did not exceed 5° C did not exceed 5° C The reaction mixture was stirred for 5 hours at a temperature between 5 and 10° C did not exceed 20° C The mixture was then stirred for 30 minutes washed a further three times with water (three times 120 1) The dichloromethane layer was then distilled to a volume of about 60 1 was added the resulting precipitate was stirred at 10° C. for 30 minutes HPLC analysis of the crude reaction mixture

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

実験手順: 4-(2'-Bromoethyl)-3-chloro-1,3-dihydro-2H-indol-2-one (23.6 g. 86 mmol), sodium hypophosphite hydrate (35 g) and 10% palladium/carbon (60% w/w wet, 2.6 g) were stirred in industrial methylated spirit (250 ml)/water (30 ml) at 80° C. The reaction was complete after 2 hours as monitored by HPLC. Inorganic components were removed by filtration and the organic solvent was removed in vaccuo. The solid residue was slurried in water (100 ml) and dried overnight to give 17.0 g (82%) of 4-(2'-bromoethyl)-1,3-dihydro-2H-indol-2-one. Inorganic components were removed by filtration the organic solvent was removed in vaccuo dried overnight

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a precooled solution of ferric chloride (28.5 kg) in dichloromethane (340 1) at 0° C. was added acetyl chloride (9.2 kg) at such a rate that the reaction temperature did not exceed 5° C. The reaction mixture was stirred at between 0° and 5° C. for 15 minutes. To the mixture was added a pre-dryed solution of 2-(2'-bromoethyl)-β-nitrostyrene [12.88 kg (16.22 kg wet:water content 20.6%)]in dichloromethane (55 litres) at such a rate that the reaction temperature did not exceed 5° C. The reaction mixture was stirred for 5 hours at a temperature between 5 and 10° C. Analysis by TLC confirmed that the reaction had gone to completion. Water (240 1) was then added to the reaction mixture at such a rate so that the temperature did not exceed 20° C. The mixture was then stirred for 30 minutes. The dichloromethane layer was isolated and washed a further three times with water (three times 120 1). The dichloromethane layer was then distilled to a volume of about 60 1. After cooling to 20° C. petroleum ether (60/80 grade. 40 1) was added and the resulting precipitate was stirred at 10° C. for 30 minutes. HPLC analysis of the crude reaction mixture indicated a purity of 93.22% of the required product. 4-(2'-bromo-ethyl)-3-chloro-1,3-dihydro-2H-indol-2-on by filtration, the filtrate washed with petroleum ether (60 1) and dried at 80° C. overnight to give 10.8 kg (78%) of of the title compound. did not exceed 5° C did not exceed 5° C The reaction mixture was stirred for 5 hours at a temperature between 5 and 10° C did not exceed 20° C The mixture was then stirred for 30 minutes washed a further three times with water (three times 120 1) The dichloromethane layer was then distilled to a volume of about 60 1 was added the resulting precipitate was stirred at 10° C. for 30 minutes HPLC analysis of the crude reaction mixture