反应详情

To a solution of 4-(1-acetyl-4-piperidinylmethyl)-2-(tert -butoxycarbonyl)-aminomethylmorpholine (Reference Example 15) (0.70 g) in methylene chloride (5 ml) was added trifluoroacetic acid (5 ml), and the mixture was stirred at room temperature for 2 hours. The reaction solution was dried under reduced pressure to be solidified, and the residue was dissolved in toluene, and then dried under reduced pressure to be solidified again. To the residue was added water, and the mixture was alkalified with 2N aqueous sodium hydroxide and extracted with chloroform. The extract was washed with water, then brine, and then dried over anhydrous magnesium sulfate. The solvent was removed in vacuo. A solution of the oily residue in DMF (5 ml) containing 4-(1-acetyl-4-piperidinylmethyl)-2-aminomethylmorpholine was added to a reaction solution which was obtained by stirring a solution of 4-amino-5-chloro-2, 3-dihydrobenzo[b]furan-7-carboxylic acid (0.42 g) and N,N′-carbonyldiimidazole (0.35 g) in DMF (10 ml) at room temperature for 1 hour. The mixture was stirred at room temperature overnight. To the reaction solution was added water, and the mixture was extracted with chloroform, and then the extract was sequentially washed with saturated sodium bicarbonate, water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed in vacuo. The residue was purified by silica gel column chromatography (eluent: chloroform/methanol=30/1) to give the titled compound (0.85 g) as a white amorphous solid.

1. customThe reaction solution was dried under reduced pressure
2. dissolutionthe residue was dissolved in toluene
3. customdried under reduced pressure
4. additionTo the residue was added water
5. extractionextracted with chloroform
6. washThe extract was washed with water
7. dry with materialbrine, and then dried over anhydrous magnesium sulfate
8. customThe solvent was removed in vacuo
9. additionA solution of the oily residue in DMF (5 ml) containing 4-(1-acetyl-4-piperidinylmethyl)-2-aminomethylmorpholine
10. additionwas added to a reaction solution which
11. customwas obtained
12. stirringThe mixture was stirred at room temperature overnight
13. extractionthe mixture was extracted with chloroform
14. washthe extract was sequentially washed with saturated sodium bicarbonate, water and brine
15. dry with materialdried over anhydrous magnesium sulfate
16. customThe solvent was removed in vacuo
17. customThe residue was purified by silica gel column chromatography (eluent: chloroform/methanol=30/1)