反应详情

To a solution of ethyl 6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-2-chloro-5-fluoronicotinate (500 mg) in ethanol (20 mL) were added ammonium formate (584 mg) and 10% Pd/C (300 mg) at 25° C. and the mixture was heated to reflux with stirring for 1 hour. After cooling, the catalyst in the reaction mixture was removed by filtration. The filtrate was evaporated in vacuo. To the residue were added CH2Cl2(30 ml), ethanol (7 mL), and benzaldehyde (140 mg) at 25° C. After stirring for 5 minutes, sodium triacetoxyborohydride (280 mg) was 3 hours, and then poured into a mixture of CH2Cl2 and aqueous NaHCO3. The organic layer was separated, dried over sodium sulfate, and concentrated in vacuo. The residue was purified by column chromatography on silica gel (11 g) using a mixed solvent of dichloromethane and MeOH (100:1 to 40:1). The fractions containing the objective compound were collected and evaporated under reduced pressure. Title compound (302 mg, 66%) was obtained as colorless syrup.

1. temperaturethe mixture was heated
2. temperatureto reflux
3. temperatureAfter cooling
4. customthe catalyst in the reaction mixture was removed by filtration
5. customThe filtrate was evaporated in vacuo
6. additionTo the residue were added CH2Cl2(30 ml), ethanol (7 mL), and benzaldehyde (140 mg) at 25° C
7. stirringAfter stirring for 5 minutes
8. waitsodium triacetoxyborohydride (280 mg) was 3 hours
9. additionpoured into a mixture of CH2Cl2 and aqueous NaHCO3
10. customThe organic layer was separated
11. dry with materialdried over sodium sulfate
12. concentrationconcentrated in vacuo
13. customThe residue was purified by column chromatography on silica gel (11 g)
14. additionThe fractions containing the objective compound
15. customwere collected
16. customevaporated under reduced pressure