4-Amino-2,3-dichlorphenol

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

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

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

Procedure: 1.55 g (0.01 mol) of chloropivaloyl chloride were added dropwise at 0° C. to a solution of 1.93 g (0.011 mol) of 4-amino-2,3-dichlorophenol in 30 ml of tetrahydrofuran, and stirring of the mixture was continued at 25° C. until starting compound was no longer detectable by thin-layer chromatography. The reaction mixture was subsequently poured into water and extracted three times using 20 ml of methylene chloride. The combined organic phases were washed twice using water, dried and concentrated. The residue was chroamtographed on silica gel (eluent: cyclohexane: ethyl acetate=2:1; yield: 0.75 g, m.p. 115° C.). was continued at 25° C. extracted three times The combined organic phases were washed twice using water dried concentrated

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 12.6 g (0.056 mol) of 1-bromo-cyclohexanecarboxylic acid chloride are added dropwise at 0° C. with stirring to a mixture of 10 g (0.056 mol) of 4-amino-2,3-dichlorophenol and 100 ml of tetrahydrofuran. After adding half (5 g) of the acid chloride, 7.7 ml (0.05 mol) of triethylamine are added dropwise at the same time. When the addition has ended, the reaction mixture is stirred for 24 hours at 20° C. and then poured into 300 ml of ice-water. The mixture is extracted twice using in each case 300 ml of dichloromethane, and the organic phase is dried over magnesium sulphate and evaporated by stripping off the solvent under reduced pressure. The residue which remains is recrystallized from toluene. In this manner. 11.9 g (58% of theory) of 4-(1-bromo-cyclohexanoyl)-amino-2,3-dichloro-phenol are obtained in the form of a solid substance of melting point 142° C. are added dropwise at the same time When the addition The mixture is extracted twice the organic phase is dried over magnesium sulphate evaporated The residue which remains is recrystallized from toluene

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

Procedure: At 0-5° C., a solution of 7.3 g (0.105 mol) of NaNO2 in 22 ml of H2O is added dropwise to 50 ml of aqueous HCl (15%) and 9.3 g (0.1 mol) of aniline in a 250 ml two-neck flask fitted with internal thermometer and magnetic stirrer. After 30 min, this diazonium salt solution is added slowly at 5-10° C. to a solution of 16.4 g (0.1 mol) of 2,3-dichlorophenol and 12.4 g (0.31 mol) of NaOH in 100 ml of H2O. The suspension is allowed to warm to room temperature and stirred for a further 1 h, and 0.5 g of Raney nickel are then added. 6 g (0.06 mol) of hydrazine hydrate are then added at 40-50° C. over a period of 2 h. After the addition, stirring is continued for 1 h and the solution is filtered over a bed of silica gel. With cooling, the solution is then adjusted to pH=5.7 with 20% strength HCl. The precipitated solid is washed with 50 ml of water and 50 ml of toluene and dried. 16.8 g (94.3% of theory) of pure 2,3-dichloro-4-hydroxyaniline are obtained. fitted with internal thermometer and magnetic stirrer After the addition stirring is continued for 1 h the solution is filtered over a bed of silica gel With cooling The precipitated solid is washed with 50 ml of water and 50 ml of toluene dried

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

Procedure: To a stirred solution of 4-amino-2,3-dichlorophenol (1.00 g, 5.62 mmol) in dry DMF (20 mL) under N2 was added K2CO3 (854 mg, 6.18 mmol) and the mixture kept at RT for 10 min and then treated with a solution of 4-chloro-3-nitropyridin-2-amine (1.024 g, 5.90 mmol) in dry DMF (5.0 mL) in a single portion. The reaction mixture was maintained at RT for 19 hr and was then partitioned between EtOAc (100 mL) and water (100 mL). The aq layer was separated and was extracted with EtOAc (4×70 mL) and the combined organic extracts were dried and evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, 80 g, EtOAc in isohexane, 0-70%, gradient elution) to afford 4-(4-amino-2,3-dichlorophenoxy)-3-nitropyridin-2-amine as a dark solid (1.28 g, 70%); Rt 1.85 min (Method 2); m/z 315 (M+H)+ (ES+). was then partitioned between EtOAc (100 mL) and water (100 mL) The aq layer was separated was extracted with EtOAc (4×70 mL) the combined organic extracts were dried evaporated in vacuo The residue was purified by flash column chromatography (SiO2, 80 g, EtOAc in isohexane, 0-70%, gradient elution)

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

Procedure: 1.55 g (0.01 mol) of chloropivaloyl chloride were added dropwise at 0° C. to a solution of 1.93 g (0.011 mol) of 4-amino-2,3-dichlorophenol in 30 ml of tetrahydrofuran, and stirring of the mixture was continued at 25° C. until starting compound was no longer detectable by thin-layer chromatography. The reaction mixture was subsequently poured into water and extracted three times using 20 ml of methylene chloride. The combined organic phases were washed twice using water, dried and concentrated. The residue was chroamtographed on silica gel (eluent: cyclohexane: ethyl acetate=2:1; yield: 0.75 g, m.p. 115° C.). was continued at 25° C. extracted three times The combined organic phases were washed twice using water dried concentrated

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 12.6 g (0.056 mol) of 1-bromo-cyclohexanecarboxylic acid chloride are added dropwise at 0° C. with stirring to a mixture of 10 g (0.056 mol) of 4-amino-2,3-dichlorophenol and 100 ml of tetrahydrofuran. After adding half (5 g) of the acid chloride, 7.7 ml (0.05 mol) of triethylamine are added dropwise at the same time. When the addition has ended, the reaction mixture is stirred for 24 hours at 20° C. and then poured into 300 ml of ice-water. The mixture is extracted twice using in each case 300 ml of dichloromethane, and the organic phase is dried over magnesium sulphate and evaporated by stripping off the solvent under reduced pressure. The residue which remains is recrystallized from toluene. In this manner. 11.9 g (58% of theory) of 4-(1-bromo-cyclohexanoyl)-amino-2,3-dichloro-phenol are obtained in the form of a solid substance of melting point 142° C. are added dropwise at the same time When the addition The mixture is extracted twice the organic phase is dried over magnesium sulphate evaporated The residue which remains is recrystallized from toluene