methyl 4-amino-3,5-dichlorobenzoate

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: 2.0 g of triethylamine were added to a solution of 4.4 g of methyl 4-amino-3,5-dichlorobenzoate in 50 ml of tetrahydrofuran and the mixture was stirred (solution 1). In parallel to this, 4.7 g of 7-methoxy-2-(1-methylethyl)benzofuran-4-carboxylic acid were stirred at 80° C. for 3 h with 10.0 ml of thionyl chloride in 40 ml of toluene and the mixture was then evaporated in vacuo. About 20 ml of toluene were added to the residue and the solution was evaporated again in vacuo. The residue was then taken up in 50 ml of tetrahydrofuran and this solution was added dropwise at RT to the prepared solution 1. After reaction was complete, the mixture was stirred into about 200 ml of ice water, treated with 30 ml of 2 N hydrochloric acid and extracted with ethyl acetate. This extract was dried over calcined sodium sulfate and evaporated in vacuo. The residue was crystallized from toluene: m.p. 175° C. the mixture was then evaporated in vacuo About 20 ml of toluene were added to the residue the solution was evaporated again in vacuo this solution was added dropwise at RT to the prepared solution 1 After reaction extracted with ethyl acetate This extract was dried evaporated in vacuo The residue was crystallized from toluene

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

実験手順: Methanol (400 ml) was added dropwise over 2 hours to a mixture of methyl-3,5-dichloro-4-aminobenzoate (110 g), NaBH4 (142.5 g) and t-butanol (1.1 L). At the end of the addition, the mixture was refluxed 3 hours, cooled, then H2O (1.2 L) was carefully added. The resulting layers were separated and the organic phase was washed with H2O (2×200 mL), separated, dried (MgSO4), filtered and evaporated to afford the desired product (89 g), mp 110-112° C. At the end of the addition the mixture was refluxed 3 hours cooled The resulting layers were separated the organic phase was washed with H2O (2×200 mL) separated dried (MgSO4) filtered evaporated

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

実験手順: Methyl 4-bromo-3,5-dichlorobenzoate: CuBr2 (7.5 g, 34.08 mmol) in MeCN (50 mL) was stirred at 80° C. for 30 min. To this solution tert-butylnitrite (6.5 mL, 54.55 mmol) was added dropwise at the same temperature and the mixture was stirred for another 10 min. Methyl 4-amino-3,5-dichlorobenzoate in MeCN (30 mL) was added dropwise to the reaction mixture which was then stirred at 80° C. for 30 min. The reaction mixture was brought to ambient temperature. Aqueous ammonia solution (20 mL) was added and extracted with petroleum ether. The organic layer was washed with brine followed by water. The organic solution was dried (Na2SO4), filtered and concentrated to afford the title compound as an off white solid (7.5 g, 77%): 1H NMR (300 MHz, DMSO-d6) δ 8.02 (s, 2H), 3.94 (s, 3H); ESIMS m/z 282 ([M]+); IR (thin film) 1733, 762, 514 cm−1. was then stirred at 80° C. for 30 min was brought to ambient temperature extracted with petroleum ether The organic layer was washed with brine The organic solution was dried (Na2SO4) filtered concentrated

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

実験手順: Methyl 4-bromo-3,5-dichlorobenzoate: CuBr2 (7.5 g, 34.08 mmol) in MeCN (50 mL) was stirred at 80° C. for 30 min. To this solution tert-butylnitrite (6.5 mL, 54.55 mmol) was added dropwise at the same temperature and the mixture was stirred for another 10 min. Methyl 4-amino-3,5-dichlorobenzoate in MeCN (30 mL) was added dropwise to the reaction mixture which was then stirred at 80° C. for 30 min. The reaction mixture was brought to ambient temperature. Aqueous ammonia solution (20 mL) was added and extracted with petroleum ether. The organic layer was washed with brine followed by water. The organic solution was dried (Na2SO4), filtered and concentrated to afford the title compound as an off white solid (7.5 g, 77%): 1H NMR (300 MHz, DMSO-d6) δ 8.02 (s, 2H), 3.94 (s, 3H); ESIMS m/z 282 ([M]+); IR (thin film) 1733, 762, 514 cm−1. was then stirred at 80° C. for 30 min was brought to ambient temperature extracted with petroleum ether The organic layer was washed with brine The organic solution was dried (Na2SO4) filtered concentrated

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

実験手順: 2.0 g of triethylamine were added to a solution of 4.4 g of methyl 4-amino-3,5-dichlorobenzoate in 50 ml of tetrahydrofuran and the mixture was stirred (solution 1). In parallel to this, 4.7 g of 7-methoxy-2-(1-methylethyl)benzofuran-4-carboxylic acid were stirred at 80° C. for 3 h with 10.0 ml of thionyl chloride in 40 ml of toluene and the mixture was then evaporated in vacuo. About 20 ml of toluene were added to the residue and the solution was evaporated again in vacuo. The residue was then taken up in 50 ml of tetrahydrofuran and this solution was added dropwise at RT to the prepared solution 1. After reaction was complete, the mixture was stirred into about 200 ml of ice water, treated with 30 ml of 2 N hydrochloric acid and extracted with ethyl acetate. This extract was dried over calcined sodium sulfate and evaporated in vacuo. The residue was crystallized from toluene: m.p. 175° C. the mixture was then evaporated in vacuo About 20 ml of toluene were added to the residue the solution was evaporated again in vacuo this solution was added dropwise at RT to the prepared solution 1 After reaction extracted with ethyl acetate This extract was dried evaporated in vacuo The residue was crystallized from toluene

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

実験手順: 2.0 g of triethylamine were added to a solution of 4.4 g of methyl 4-amino-3,5-dichlorobenzoate in 50 ml of tetrahydrofuran and the mixture was stirred (solution 1). In parallel to this, 4.7 g of 7-methoxy-2-(1-methylethyl)benzofuran-4-carboxylic acid were stirred at 80° C. for 3 h with 10.0 ml of thionyl chloride in 40 ml of toluene and the mixture was then evaporated in vacuo. About 20 ml of toluene were added to the residue and the solution was evaporated again in vacuo. The residue was then taken up in 50 ml of tetrahydrofuran and this solution was added dropwise at RT to the prepared solution 1. After reaction was complete, the mixture was stirred into about 200 ml of ice water, treated with 30 ml of 2 N hydrochloric acid and extracted with ethyl acetate. This extract was dried over calcined sodium sulfate and evaporated in vacuo. The residue was crystallized from toluene: m.p. 175° C. the mixture was then evaporated in vacuo About 20 ml of toluene were added to the residue the solution was evaporated again in vacuo this solution was added dropwise at RT to the prepared solution 1 After reaction extracted with ethyl acetate This extract was dried evaporated in vacuo The residue was crystallized from toluene

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: Methyl-4-amino-3,5-dichlorobenzoate (16.8 g, 31 mmole), 1-acetyl-2-imidazolidone (4.3 g, 33.5 mmole) in phosphoryl chloride (44 ml) were stirred at 50° C. for 3 days. After cooling the phosphoryl chloride was evaporated to give an oily residue. Iced water was added to the residue which was then basified with aqueous sodium hydroxide. The mixture was extracted with methylene chloride which was then washed with water, dried (magnesium sulphate) and evaporated to give a creamy solid. This solid was recrystallised from toluene to give the title compound (7.7 g) mp 188°-189° C. was evaporated to give an oily residue The mixture was extracted with methylene chloride which was then washed with water dried (magnesium sulphate) evaporated to give a creamy solid This solid was recrystallised from toluene

反応条件: temp:250.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 0.2 mole=48 g of methyl 3,5-dichloro-4-amino-benzoate were initially introduced into an autoclave together with 250 ml of water. The mixture was heated to 250° C. and stirred at this temperature for 3 hours. Reaction gas formed was continuously let off to maintain a pressure of about 40 bar. The product was recovered by steam distillation. 26.9 g of 2,6-dichloroaniline were obtained, corresponding to a yield of 75.3%. Reaction gas formed to maintain a pressure of about 40 bar The product was recovered by steam distillation