2-amino-3-chlorophenol

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

Procedure: 143.6 g (1 mol) of 5-chloro-2-aminophenol, 164 g (1.02 mols) of sodium methyl xanthate (90% strength) and 500 ml of water were introduced into a 1 liter flask equipped with stirrer, thermometer and reflux condenser. The reaction mixture (the chloro-aminophenol remained undissolved) was warmed with stirring, from 80° C. on vigorous hydrogen sulfide development occured. After about 1 hour the reaction was essentially complete, but stirring with reflux was continued for a further 2 hours. The resulting black reaction solution was cooled, and acidified with 70 g of 85% phosphoric acid. The precipitate was suction-filtered, washed thoroughly with water and subsequently dried at about 80° C. under reduced pressure. After drying, 180.5 g (97.3% of th.) of 6-chloro-2-mercaptobenzoxazole having a melting point of 221°-223° C. were obtained. (The literature gives a m.p. of 224°-225° C. after recrystallization from water/isopropanol, J. org. Chem. 19, 758). According to gas chromatography, the purity degree of the product was higher than 98%. equipped with stirrer thermometer and reflux condenser with reflux was continued for a further 2 hours The resulting black reaction solution was cooled The precipitate was suction-filtered washed thoroughly with water subsequently dried at about 80° C. under reduced pressure After drying

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-chloro-2-nitrophenol(250 mg, 1.4 mmol) and tin (II) chloride (1.2 g, 5.3 mmol) in ethanol(50 mL) was heated at 80° C. under argon. After 2 hours, the starting material has disappeared and the solution was allowed to cool down and then poured into ice. The pH was made slightly basic (pH7-8), by addition of solid NaOH, before being extracted with ethyl acetate. The organic phase was washed with brine, dried over MgSO4 and filtered. The solvent was evaporated and chromatography of the resulting solid on silica gel (4% MeOH/CH2Cl2) gave the desired product(143 mg, 69%). 1H NMR (CD3OD): d 6.75 (t,1H), 6.70 (d, 1H), 6.65 (d, 1H). to cool down poured into ice before being extracted with ethyl acetate The organic phase was washed with brine dried over MgSO4 filtered The solvent was evaporated

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-chloro-2-nitrophenol(250 mg, 1.4 mmol) and tin (II) chloride (1.2 g, 5.3 mmol) in ethanol(50 mL) was heated at 80° C. under argon. After 2 hours, the starting material has disappeared and the solution was allowed to cool down and then poured into ice. The pH was made slightly basic (pH7-8), by addition of solid NaOH, before being extracted with ethyl acetate. The organic phase was washed with brine, dried over MgSO4 and filtered. The solvent was evaporated and chromatography of the resulting solid on silica gel (4%MeOH/CH2Cl2) gave the desired product(143 mg, 69%). 1H NMR (CD3OD): δ 6.75 (t, 1H), 6.70 (d, 1H), 6.65 (d, 1H). to cool down poured into ice before being extracted with ethyl acetate The organic phase was washed with brine dried over MgSO4 filtered The solvent was evaporated

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-chloro-2-nitrophenol(250 mg, 1.4 mmol) and tin (II) chloride (1.2 g, 5.3 mmol) in ethanol(50 mL) was heated at 80° C. under argon. After 2 hours, the starting material has disappeared and the solution was allowed to cool down and then poured into ice. The pH was made slightly basic (pH7-8), by addition of solid NaOH, before being extracted with ethyl acetate. The organic phase was washed with brine, dried over MgSO4 and filtered. The solvent was evaporated and chromatography of the resulting solid on silica gel (4%MeOH/CH2Cl2) gave the desired product(143 mg, 69%). 1H NMR (CD3OD): δ 6.75 (t, 1H), 6.70 (d, 1H), 6.65 (d, 1H). to cool down poured into ice before being extracted with ethyl acetate The organic phase was washed with brine dried over MgSO4 filtered The solvent was evaporated

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

Procedure: Using an analogous procedure to that described in Example 286, 248.7 mg (1 mmol) of 4-chloro-6,7-dimethoxy-3-quinolinecarbonitrile in 15 mL of 2-ethoxyethanol and in the presence of 115.6 mg (1 mmol) of pyridine hydrochloride was reacted with 172.3 mg (1.2 mmol) of 2-amino-chlorophenol to give 326.4 mg (91.9%) of the product as a yellow solid, m.p.>250° C., mass (electrospray, m/e): M+H 355.8.

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

Procedure: Using an analogous procedure to that described in Example 286, 248.7 mg (1 mmol) of 4-chloro-6,7-dimethoxy-3-quinolinecarbonitrile in 15 mL of 2-ethoxyethanol and in the presence of 115.6 mg (1 mmol) of pyridine hydrochloride was reacted with 172.3 mg (1.2 mmol) of 2-amino-chlorophenol to give 326.4 mg (91.9%) of the product as a yellow solid, m.p.>250° C., mass (electrospray, m/e): M+H 355.8.

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-chloro-2-nitrophenol(250 mg, 1.4 mmol) and tin (II) chloride (1.2 g, 5.3 mmol) in ethanol(50 mL) was heated at 80° C. under argon. After 2 hours, the starting material has disappeared and the solution was allowed to cool down and then poured into ice. The pH was made slightly basic (pH7-8), by addition of solid NaOH, before being extracted with ethyl acetate. The organic phase was washed with brine, dried over MgSO4 and filtered. The solvent was evaporated and chromatography of the resulting solid on silica gel (4% MeOH/CH2Cl2) gave the desired product(143 mg, 69%). 1H NMR (CD3OD): δ 6.75 (t,1H), 6.70 (d, 1H), 6.65 (d, 1H). to cool down poured into ice before being extracted with ethyl acetate The organic phase was washed with brine dried over MgSO4 filtered The solvent was evaporated

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

Procedure: 143.6 g (1 mol) of 5-chloro-2-aminophenol, 164 g (1.02 mols) of sodium methyl xanthate (90% strength) and 500 ml of water were introduced into a 1 liter flask equipped with stirrer, thermometer and reflux condenser. The reaction mixture (the chloro-aminophenol remained undissolved) was warmed with stirring, from 80° C. on vigorous hydrogen sulfide development occured. After about 1 hour the reaction was essentially complete, but stirring with reflux was continued for a further 2 hours. The resulting black reaction solution was cooled, and acidified with 70 g of 85% phosphoric acid. The precipitate was suction-filtered, washed thoroughly with water and subsequently dried at about 80° C. under reduced pressure. After drying, 180.5 g (97.3% of th.) of 6-chloro-2-mercaptobenzoxazole having a melting point of 221°-223° C. were obtained. (The literature gives a m.p. of 224°-225° C. after recrystallization from water/isopropanol, J. org. Chem. 19, 758). According to gas chromatography, the purity degree of the product was higher than 98%. equipped with stirrer thermometer and reflux condenser with reflux was continued for a further 2 hours The resulting black reaction solution was cooled The precipitate was suction-filtered washed thoroughly with water subsequently dried at about 80° C. under reduced pressure After drying

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

Procedure: 143.6 g (1 mol) of 5-chloro-2-aminophenol, 164 g (1.02 mols) of sodium methyl xanthate (90% strength) and 500 ml of water were introduced into a 1 liter flask equipped with stirrer, thermometer and reflux condenser. The reaction mixture (the chloro-aminophenol remained undissolved) was warmed with stirring, from 80° C. on vigorous hydrogen sulfide development occured. After about 1 hour the reaction was essentially complete, but stirring with reflux was continued for a further 2 hours. The resulting black reaction solution was cooled, and acidified with 70 g of 85% phosphoric acid. The precipitate was suction-filtered, washed thoroughly with water and subsequently dried at about 80° C. under reduced pressure. After drying, 180.5 g (97.3% of th.) of 6-chloro-2-mercaptobenzoxazole having a melting point of 221°-223° C. were obtained. (The literature gives a m.p. of 224°-225° C. after recrystallization from water/isopropanol, J. org. Chem. 19, 758). According to gas chromatography, the purity degree of the product was higher than 98%. equipped with stirrer thermometer and reflux condenser with reflux was continued for a further 2 hours The resulting black reaction solution was cooled The precipitate was suction-filtered washed thoroughly with water subsequently dried at about 80° C. under reduced pressure After drying

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-chloro-2-nitrophenol(250 mg, 1.4 mmol) and tin (II) chloride (1.2 g, 5.3 mmol) in ethanol(50 mL) was heated at 80° C. under argon. After 2 hours, the starting material has disappeared and the solution was allowed to cool down and then poured into ice. The pH was made slightly basic (pH7-8), by addition of solid NaOH, before being extracted with ethyl acetate. The organic phase was washed with brine, dried over MgSO4 and filtered. The solvent was evaporated and chromatography of the resulting solid on silica gel (4% MeOH/CH2Cl2) gave the desired product(143 mg, 69%). 1H NMR (CD3OD): d 6.75 (t,1H), 6.70 (d, 1H), 6.65 (d, 1H). to cool down poured into ice before being extracted with ethyl acetate The organic phase was washed with brine dried over MgSO4 filtered The solvent was evaporated

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-chloro-2-nitrophenol(250 mg, 1.4 mmol) and tin (II) chloride (1.2 g, 5.3 mmol) in ethanol(50 mL) was heated at 80° C. under argon. After 2 hours, the starting material has disappeared and the solution was allowed to cool down and then poured into ice. The pH was made slightly basic (pH7-8), by addition of solid NaOH, before being extracted with ethyl acetate. The organic phase was washed with brine, dried over MgSO4 and filtered. The solvent was evaporated and chromatography of the resulting solid on silica gel (4% MeOH/CH2Cl2) gave the desired product(143 mg, 69%). 1H NMR (CD3OD): d 6.75 (t,1H), 6.70 (d, 1H), 6.65 (d, 1H). to cool down poured into ice before being extracted with ethyl acetate The organic phase was washed with brine dried over MgSO4 filtered The solvent was evaporated

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-chloro-2-nitrophenol(250 mg, 1.4 mmol) and tin (II) chloride (1.2 g, 5.3 mmol) in ethanol(50 mL) was heated at 80° C. under argon. After 2 hours, the starting material has disappeared and the solution was allowed to cool down and then poured into ice. The pH was made slightly basic (pH7-8), by addition of solid NaOH, before being extracted with ethyl acetate. The organic phase was washed with brine, dried over MgSO4 and filtered. The solvent was evaporated and chromatography of the resulting solid on silica gel (4%MeOH/CH2 Cl2) gave the desired product(143 mg, 69%). 1H NMR (CD3 OD): d 6.75 (t,1H), 6.70 (d, 1H), 6.65 (d, 1H). to cool down poured into ice before being extracted with ethyl acetate The organic phase was washed with brine dried over MgSO4 filtered The solvent was evaporated