反应详情

A mixture (3-formyl-phenyl)-acetic acid ethyl ester (530 mg), (3-propoxypropyl)amine (1.5 g) and acetic acid (0.17 mL) in methanol (15 mL) was stirred at room temperature for 15 minutes. Sodium triacetoxyborohydride (950 mg) was added. After 5 hours, the reaction mixture was neutralised with aqueous ammonia (0.880) and the solution evaporated to dryness. The residue was diluted with toluene and the mixture evaporated. The resulting gum was dissolved in methanol and applied to a SCX cartridge (70 g, varian). The cartridge was eluted with methanol (250 mL) and then 20% ammonia in methanol to collect the reductive amination product. Toluene was added and the solution was evaporated. The crude product was dissolved in dichloromethane (20 mL) and di-tert-butyl dicarbonate (1.8 g) added. After 16 hours, the solution was evaporated, the residue dissolved in ethanol (30 mL), anhydrous calcium chloride (11.0 g) added, followed by portionwise addition of sodium borohydride (700 mg). After 16 hours, the reaction mixture was quenched with 2M aqueous potassium carbonate (20 mL), filtered and evaporated. The residue was partitioned between ethyl acetate and brine. The organic solution was dried over sodium sulphate, filtered and evaporated. Purification was by silica gel chromatography eluting with ethyl acetate:dichloromethane 1:4 to give the subtitle compound (300 mg).

1. customthe solution evaporated to dryness
2. additionThe residue was diluted with toluene
3. customthe mixture evaporated
4. dissolutionThe resulting gum was dissolved in methanol
5. washThe cartridge was eluted with methanol (250 mL)
6. custom20% ammonia in methanol to collect the reductive amination product
7. additionToluene was added
8. customthe solution was evaporated
9. dissolutionThe crude product was dissolved in dichloromethane (20 mL)
10. additiondi-tert-butyl dicarbonate (1.8 g) added
11. waitAfter 16 hours
12. customthe solution was evaporated
13. dissolutionthe residue dissolved in ethanol (30 mL)
14. additionanhydrous calcium chloride (11.0 g) added
15. additionfollowed by portionwise addition of sodium borohydride (700 mg)
16. waitAfter 16 hours
17. customthe reaction mixture was quenched with 2M aqueous potassium carbonate (20 mL)
18. filtrationfiltered
19. customevaporated
20. customThe residue was partitioned between ethyl acetate and brine
21. dry with materialThe organic solution was dried over sodium sulphate
22. filtrationfiltered
23. customevaporated
24. customPurification
25. washeluting with ethyl acetate:dichloromethane 1:4