反应详情

In 60 ml of methylene chloride was dissolved 4.00 g of ethyl 4-(2-hydroxymethylcyclopropyl)-2,3,5trifluorobenzoate. To the resulting solution were added 1.62 g of triethylamine and 1.84 g of methanesulfonyl chloride in this order with ice-cooling. The resulting mixture was stirred at room temperature for 2 hours, and 60 ml of water was added to the reaction mixture. The resulting mixture was adjusted to pH 1 with 2N hydrochloric acid. The organic layer was separated, washed with water, a saturated aqueous sodium hydrogencarbonate solution and a saturated aqueous sodium chloride solution in this order, and dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure. The residue obtained was dissolved in 60 ml of N,N-dimethylformamide. To the resulting solution was added 3.42 g of potassium salt of tert-butyl methyliminodicarboxylate with ice-cooling. The resulting mixture was stirred at room temperature for 48 hours. The reaction mixture was added to a mixture of 100 ml of ethyl acetate and 100 ml of water. The resulting mixture was adjusted to pH 1.5 with 2N hydrochloric acid. The organic layer was separated, washed with water and a saturated aqueous sodium chloride solution in this order, and dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure. The residue obtained was purified by a column chromatography (eluant: toluene/ ethyl acetate=20/1) to obtain 5.22 g (yield: 82.9%) of ethyl 4-[2-(N-tert-butoxycarbonyl-N-methoxycarbonylaminomethyl)cyclopropyl]-2,3,5-trifluorobenzoate.

1. temperaturecooling
2. customThe organic layer was separated
3. washwashed with water
4. dry with materiala saturated aqueous sodium hydrogencarbonate solution and a saturated aqueous sodium chloride solution in this order, and dried over anhydrous magnesium sulfate
5. customThe solvent was removed by distillation under reduced pressure
6. customThe residue obtained
7. temperaturecooling
8. stirringThe resulting mixture was stirred at room temperature for 48 hours
9. customThe organic layer was separated
10. washwashed with water
11. dry with materiala saturated aqueous sodium chloride solution in this order, and dried over anhydrous magnesium sulfate
12. customThe solvent was removed by distillation under reduced pressure
13. customThe residue obtained
14. customwas purified by a column chromatography (eluant: toluene/ ethyl acetate=20/1)