4-chloro-2-fluorophenol

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:

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:

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

実験手順: A mixture of 4-chloro-6-methoxy-7-(2-([1,2,4]-triazol-1-yl)ethoxy)quinoline (132 mg, 0.43 mmol), 4-chloro-2-fluorophenol (400 mg, 2.7 mmol) and potassium hydroxide (28 mg, 0.49 mmol) was head at 165° C. for 3 hours under argon. The mixture was partitioned between ethyl acetate and water. The organic layer was washed with water, brine, dried (MgSO4) and the volatiles were removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol (95/5). The purified product was dissolved in methylene chloride and 2M ethereal hydrogen chloride (0.5 ml) was added. The volatiles were removed by evaporation and the residue was triturated with ether, collected by filtration and dried under vacuum to give 4-(4-chloro-2-fluorophenoxy)-6-methoxy-7-(2-([1,2,4]-triazol-1-yl)ethoxy)quinoline hydrochloride (110 mg, 61%). at 165° C. for 3 hours The mixture was partitioned between ethyl acetate and water The organic layer was washed with water, brine dried (MgSO4) the volatiles were removed by evaporation The residue was purified by column chromatography eluting with methylene chloride/methanol (95/5) The purified product was dissolved in methylene chloride 2M ethereal hydrogen chloride (0.5 ml) was added The volatiles were removed by evaporation the residue was triturated with ether collected by filtration dried under vacuum

反応条件: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The procedure of a) was used except that 0.64 g of 4-chlorophenol was employed, the fluorinating agent was 1.89 g of N-fluoro-2,3-dichloro-6-(trichloromethyl)pyridinium fluoroborate, and 40 ml of solvent was employed. There was a slight exotherm on mixing. The mixture was heated to 45° C. and allowed to react at that temperature for 3 hours. The mixture was then allowed to cool and the volatiles were removed by evaporation under reduced pressure. Analysis of the residue by standardized gas-liquid chromatography using a mass spectrometer detector indicated that the title product was present in 69 percent yield. on mixing to react at that temperature for 3 hours to cool the volatiles were removed by evaporation under reduced pressure

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:

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

実験手順: 4-Chloro-2-fluoro-phenol (264 mg, 1.8 mmol) was added to a solution of 7-benzyloxy-4-chloro-6-methoxyquinazoline hydrochloride (506 mg, 1.5 mmol), (prepared as described for the starting material in Example 1), in pyridine (8 ml) and the mixture heated at reflux for 45 minutes. The solvent was removed by evaporation and the residue partitioned between ethyl acetate and water. The organic layer was washed with 0.1M hydrochloric acid, water and brine, dried (MgSO4) and the solvent removed by evaporation. The solid residue was triturated with petroleum ether and the crude product collected by filtration and purified by flash chromatography eluting with methylene chloride/ether (9/1) to give 7-benzyloxy-4-(4-chloro-2-fluorophenoxy)-6-methoxyquinazoline (474 mg, 77%) as a cream solid. (prepared the mixture heated at reflux for 45 minutes The solvent was removed by evaporation the residue partitioned between ethyl acetate and water The organic layer was washed with 0.1M hydrochloric acid, water and brine dried (MgSO4) the solvent removed by evaporation The solid residue was triturated with petroleum ether the crude product collected by filtration purified by flash chromatography eluting with methylene chloride/ether (9/1)