反应详情

温度

50 °C

0.33 g (1.0 mmol) of 2-methyl-2-[3-(piperidin-4-ylcarbamoyl)-phenoxy]-propionic acid ethyl ester and 0.23 g (1.10 eq.) of 3,5-diethoxy-4-fluoro-benzaldehyde (example 50 g), were dissolved under argon in 6 mL of MeOH; 0.39 mL (0.29 g=2.25 eq.) of N-ethyl-diisopropylamine and 0.11 mL (0.12 g=2.0 eq.) of glacial acetic acid were added and the mixture then heated for 2 h at 50° C. After cooling down to rt, 0.16 g (2.5 eq.) of sodium cyanoborohydride was added and the reaction mixture heated again for 1.5 h at 50° C. It was then poured into crashed ice, the pH was adjusted to ˜10 with sodium carbonate solution and the mixture was extracted twice with MeCl2; the organic phases were washed with water, dried over MgSO4, filtered and evaporated i.V. The crude product was purified by chromatography (silicagel, eluent:gradient of MeCl2/MeOH) to yield 0.50 g of the title compound as colorless oil. MS: 531.2 (MH+).

1. temperatureAfter cooling down to rt
2. temperaturethe reaction mixture heated again for 1.5 h at 50° C
3. additionIt was then poured
4. extractionthe mixture was extracted twice with MeCl2
5. washthe organic phases were washed with water
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. customevaporated i.V
9. customThe crude product was purified by chromatography (silicagel, eluent:gradient of MeCl2/MeOH)