ethyl N-(4-bromo-2-fluorophenyl)carbamate

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

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Ethyl chloroformate (15.91 g) was added dropwise to a solution of 4-bromo-2-fluoroaniline (25.33 g) and pyridine (21.06 g) in methylene chloride (260 ml) at 0° C., and the mixture was stirred at 10° C. for 3 hours. After the reaction, it was extracted with methylene chloride, then washed with diluted hydrochloric acid and an aqueous sodium hydrogencarbonate solution, and dried over anhydrous magnesium sulfate. Then, methylene chloride was distilled off, and the resulting crude crystals were crystallized from ethyl acetate-n-hexane (1:5 v/v) to obtain the objective ethyl N-(4-bromo-2-fluorophenyl)carbamate (34.45 g). After the reaction, it was extracted with methylene chloride washed with diluted hydrochloric acid an aqueous sodium hydrogencarbonate solution, and dried over anhydrous magnesium sulfate Then, methylene chloride was distilled off the resulting crude crystals were crystallized from ethyl acetate-n-hexane (1:5 v/v)

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Ethyl 3-amino-4,4,4-trifluoro-2-methylcrotonate (26.0 g) was dissolved in DMF (123 ml). To this solution, a suspension of sodium methoxide in DNF (7.78 g) was added dropwise at 0° C., and the mixture was stirred at 5° C. for 30 minutes. Then, a DMF solution of ethyl N-(4-bromo-2-fluoro-phenyl)carbamate (31.44 g) was added dropwise thereto, and the mixture was stirred at 130° C. for 5 hours. After the reaction, DMF was distilled off under reduced pressure, and the residue was acidified by adding diluted hydrochloric acid thereto. This was extracted with ethyl acetate, washed with water, and then dried over anhydrous magnesium sulfate. Ethyl acetate was distilled off, and the resulting residue was crystallized from ethyl acetate-n-hexane (1:3 v/v) to obtain the objective 3-(4-bromo-2-fluorophenyl)-5-methyl-6-trifluoromethyl-2,4(1H,3H)-pyrimidinedione (18.78 g). was added dropwise at 0° C. the mixture was stirred at 130° C. for 5 hours was distilled off under reduced pressure by adding diluted hydrochloric acid This was extracted with ethyl acetate washed with water dried over anhydrous magnesium sulfate Ethyl acetate was distilled off the resulting residue was crystallized from ethyl acetate-n-hexane (1:3 v/v)

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

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Ethyl chloroformate (15.91 g) was added dropwise to a solution of 4-bromo-2-fluoroaniline (25.33 g) and pyridine (21.06 g) in methylene chloride (260 ml) at 0° C., and the mixture was stirred at 10° C. for 3 hours. After the reaction, it was extracted with methylene chloride, then washed with diluted hydrochloric acid and an aqueous sodium hydrogencarbonate solution, and dried over anhydrous magnesium sulfate. Then, methylene chloride was distilled off, and the resulting crude crystals were crystallized from ethyl acetate-n-hexane (1:5 v/v) to obtain the objective ethyl N-(4-bromo-2-fluorophenyl)carbamate (34.45 g). After the reaction, it was extracted with methylene chloride washed with diluted hydrochloric acid an aqueous sodium hydrogencarbonate solution, and dried over anhydrous magnesium sulfate Then, methylene chloride was distilled off the resulting crude crystals were crystallized from ethyl acetate-n-hexane (1:5 v/v)

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Ethyl 3-amino-4,4,4-trifluoro-2-methylcrotonate (26.0 g) was dissolved in DMF (123 ml). To this solution, a suspension of sodium methoxide in DNF (7.78 g) was added dropwise at 0° C., and the mixture was stirred at 5° C. for 30 minutes. Then, a DMF solution of ethyl N-(4-bromo-2-fluoro-phenyl)carbamate (31.44 g) was added dropwise thereto, and the mixture was stirred at 130° C. for 5 hours. After the reaction, DMF was distilled off under reduced pressure, and the residue was acidified by adding diluted hydrochloric acid thereto. This was extracted with ethyl acetate, washed with water, and then dried over anhydrous magnesium sulfate. Ethyl acetate was distilled off, and the resulting residue was crystallized from ethyl acetate-n-hexane (1:3 v/v) to obtain the objective 3-(4-bromo-2-fluorophenyl)-5-methyl-6-trifluoromethyl-2,4(1H,3H)-pyrimidinedione (18.78 g). was added dropwise at 0° C. the mixture was stirred at 130° C. for 5 hours was distilled off under reduced pressure by adding diluted hydrochloric acid This was extracted with ethyl acetate washed with water dried over anhydrous magnesium sulfate Ethyl acetate was distilled off the resulting residue was crystallized from ethyl acetate-n-hexane (1:3 v/v)