4-tert-butyl-2-fluoroaniline

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

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

Procedure: 4-t-Butyl-2-fluoroaniline (4.79 g) prepared according to the above process and ethyl 2-methyl-acetoacetate (4.96 g) were refluxed in toluene (60 ml) in the presence of trifluoroboron etherate (0.3 ml) for 3 hr to obtain a reaction solution. The reaction solution thus obtained was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine and was dried over anhydrous sodium sulfate. The solvent was then removed under the reduced pressure. The reaction product was refluxed in diphenyl ether (80 ml) for one hr and was allowed to stand for cooling. The precipitated product was then collected by filtration under the reduced pressure to give 2,3-dimethyl-6-t-butyl-8-fluoro-4-hydroxyquinoline (compound 1, 1.66 g). 1H-NMR data on this compound in deutro-DMSO (dimethyl sulfoxide) were as shown below. to obtain a reaction solution The reaction solution thus obtained was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine was dried over anhydrous sodium sulfate The solvent was then removed under the reduced pressure The reaction product was refluxed in diphenyl ether (80 ml) for one hr for cooling The precipitated product was then collected by filtration under the reduced pressure

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

Procedure: 4-t-Butyl-2-fluoroaniline (4.79 g) prepared according to the above process and ethyl 2-methyl-acetoacetate (4.96 g) were refluxed in toluene (60 ml) in the presence of trifluoroboron etherate (0.3 ml) for 3 hr to obtain a reaction solution. The reaction solution thus obtained was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine and was dried over anhydrous sodium sulfate. The solvent was then removed under the reduced pressure. The reaction product was refluxed in diphenyl ether (80 ml) for one hr and was allowed to stand for cooling. The precipitated product was then collected by filtration under the reduced pressure to give 2,3-dimethyl-6-t-butyl-8-fluoro-4-hydroxyquinoline (compound 1, 1.66 g). 1H-NMR data on this compound in deutro-DMSO (dimethyl sulfoxide) were as shown below. to obtain a reaction solution The reaction solution thus obtained was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine was dried over anhydrous sodium sulfate The solvent was then removed under the reduced pressure The reaction product was refluxed in diphenyl ether (80 ml) for one hr for cooling The precipitated product was then collected by filtration under the reduced pressure

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

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 303 g of 4-t-butyl-2-fluoro-N-methoxycarbonylaniline as the crude product was added 657 g of a 30% aqueous sodium hydroxide solution. The mixture was heated under reflux at a temperature around 90° C. for 4 hr and was allowed to cool. Water (1,000 mL) was then added thereto, and the mixture was extracted four times with 500 mL of hexane. The organic layers thus obtained were combined, and 2 M hydrochloric acid was added thereto, followed by vigorous stirring to convert the amino group to a hydrochloride form. Subsequently, an aqueous layer was separated and was adjusted to pH 9 by the addition of aqueous sodium hydroxide solution to bring the amino group to a free form. Extraction was carried out twice with 1,000 mL of toluene. The organic layers thus obtained were combined, and the combined organic layer was washed with saturated brine. The solvent was then removed from the organic layer by distillation to give 92.9 g of 4-t-butyl-2-fluoroaniline as an oily substantially single product (yield 65.6% (yield in two steps of t-butylation-deprotection)). The mixture was heated to cool the mixture was extracted four times with 500 mL of hexane The organic layers thus obtained Subsequently, an aqueous layer was separated was adjusted to pH 9 by the addition of aqueous sodium hydroxide solution Extraction The organic layers thus obtained the combined organic layer was washed with saturated brine The solvent was then removed from the organic layer by distillation

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

Procedure: 4-t-Butyl-2-fluoroaniline (4.79 g) prepared according to the above process and ethyl 2-methyl-acetoacetate (4.96 g) were refluxed in toluene (60 ml) in the presence of trifluoroboron etherate (0.3 ml) for 3 hr to obtain a reaction solution. The reaction solution thus obtained was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine and was dried over anhydrous sodium sulfate. The solvent was then removed under the reduced pressure. The reaction product was refluxed in diphenyl ether (80 ml) for one hr and was allowed to stand for cooling. The precipitated product was then collected by filtration under the reduced pressure to give 2,3-dimethyl-6-t-butyl-8-fluoro-4-hydroxyquinoline (compound 1, 1.66 g). 1H-NMR data on this compound in deutro-DMSO (dimethyl sulfoxide) were as shown below. to obtain a reaction solution The reaction solution thus obtained was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine was dried over anhydrous sodium sulfate The solvent was then removed under the reduced pressure The reaction product was refluxed in diphenyl ether (80 ml) for one hr for cooling The precipitated product was then collected by filtration under the reduced pressure