5-chloro-2-methoxyaniline

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

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

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: In the manner described in example 3, 2-bromophenylacetic acid is condensed with 2-methoxy-5-chloroaniline to yield 2-[(2-methoxy-5-chlorophenyl)amino]phenylacetic acid.

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

Procedure: In the manner described in example 3, 2-bromophenylacetic acid is condensed with 2-methoxy-5-chloroaniline to yield 2-[(2-methoxy-5-chlorophenyl)amino]phenylacetic acid.

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of sodium nitrite (57 mg, 0.8 mmol) in water (1 mL) was added to a solution of 2-amino-4-chloroanisole (131 mg, 0.8 mmol) in 48% hydrogen tetrafluoroborate (0.3 mL) under ice cooling and argon atmosphere. After the mixture was stirred at 0° C. for 1 hour, a solution of 3,5-bis(trifluoromethyl)styrene (100 mg, 0.4 mmol) in methanol (3 mL) was added and the mixture was stirred at 50° C. for 1 hour. After the reaction mixture was cooled to room temperature, the residue obtained by evaporation of the solvent under reduced pressure was diluted with ethyl acetate. After the solution was washed successively with 2N hydrochloric acid, water and brine, dried over anhydrous sodium sulfate, the residue obtained by evaporation of the solvent under reduced pressure was purified by column chromatography on silica gel (n-hexane:ethyl acetate=5:1) to give the title compound (52.8 mg, 33.3%) as a white powder. the mixture was stirred at 50° C. for 1 hour After the reaction mixture was cooled to room temperature the residue obtained by evaporation of the solvent under reduced pressure After the solution was washed successively with 2N hydrochloric acid, water and brine dried over anhydrous sodium sulfate the residue obtained by evaporation of the solvent under reduced pressure was purified by column chromatography on silica gel (n-hexane:ethyl acetate=5:1)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of sodium nitrite (57 mg, 0.8 mmol) in water (1 mL) was added to a solution of 2-amino-4-chloroanisole (131 mg, 0.8 mmol) in 48% hydrogen tetrafluoroborate (0.3 mL) under ice cooling and argon atmosphere. After the mixture was stirred at 0° C. for 1 hour, a solution of 3,5-bis(trifluoromethyl)styrene (100 mg, 0.4 mmol) in methanol (3 mL) was added and the mixture was stirred at 50° C. for 1 hour. After the reaction mixture was cooled to room temperature, the residue obtained by evaporation of the solvent under reduced pressure was diluted with ethyl acetate. After the solution was washed successively with 2N hydrochloric acid, water and brine, dried over anhydrous sodium sulfate, the residue obtained by evaporation of the solvent under reduced pressure was purified by column chromatography on silica gel (n-hexane:ethyl acetate=5:1) to give the title compound (52.8 mg, 33.3%) as a white powder. the mixture was stirred at 50° C. for 1 hour After the reaction mixture was cooled to room temperature the residue obtained by evaporation of the solvent under reduced pressure After the solution was washed successively with 2N hydrochloric acid, water and brine dried over anhydrous sodium sulfate the residue obtained by evaporation of the solvent under reduced pressure was purified by column chromatography on silica gel (n-hexane:ethyl acetate=5:1)

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

Procedure: A solution of 10 gm (44 millimols) of 4-hydroxy-4'-biphenyl-acetic acid (see W. H. Linnell and H. J. Smith, J. Chem. Soc. 1959,557) in a mixture of 33 ml of tetrahydrofuran and 162 ml of absolute dioxane were added at 0° C to a solution of 4.63 gm (29.4 millimols) of 2-methoxy-5-chloroaniline (m.p. 83°-85° C) in 40 ml of absolute dioxane, and the mixed solution was subsequently admixed with a solution of 9.1 gm (44 millimols) of N,N'-dicyclohexyl-carbodiimide in 20 ml of dioxane. After 20 hours of reaction time at 0° C, the dicyclohexylurea was filtered off and the solvent was distilled off. The residue was dissolved in 700 ml of chloroform, the solution was washed several times with 2N hydrochloric acid and water, dried over sodium sulfate, and the organic phase was evaporated in vacuo. The light brown, viscous crude product was purified on a silicagel column with toluene/acetic acid (4:1 ) as the eluant. Yield: 70% of theory; m.p. 165°-168° C. After 20 hours of reaction time at 0° C the dicyclohexylurea was filtered off the solvent was distilled off The residue was dissolved in 700 ml of chloroform the solution was washed several times with 2N hydrochloric acid and water dried over sodium sulfate the organic phase was evaporated in vacuo The light brown, viscous crude product was purified on a silicagel column with toluene/acetic acid (4:1 ) as the eluant

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

Procedure: In the manner described in example 3, 2-bromophenylacetic acid is condensed with 2-methoxy-5-chloroaniline to yield 2-[(2-methoxy-5-chlorophenyl)amino]phenylacetic acid.

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

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