Benzaldehyde → HCID 58310981, Verbindung

Temperatur

35 °C

A 250 ml round bottom flask equipped with a stir bar and an addition funnel was charged with sodium cyanide (1.386 g, 28.3 mmol) and DMF (20 ml). The flask was placed in an oil bath at 35° C. To this suspension at 35° C., was added over the course of 30 minutes, solution of benzaldehyde (5.55 ml, 54.8 mmol) in DMF (20.00 ml). The mixture was stirred at 35° C. for an additional 1.5 h. To this mixture, was added over the course of 2 hours, a solution of (E)-4-(3-fluorophenyl)but-3-en-2-one (6.92 g, 42.1 mmol) in DMF (20 ml). The mixture was stirred at 35° C. overnight. The mixture was quenched with water (100 ml×2) and extracted with ethyl acetate (200 ml). The organic layer was washed with water (100 ml×3) and brine (100 ml). The combined organic layers were dried, filtered, and evaporated to give an oil. The oil was combined with ethyl 2-aminoacetate hydrochloride (4.03 g, 28.9 mmol), triethylamine (6.03 ml, 43.3 mmol) and EtOH (26.2 ml) and the resulting mixture was heated at 100° C. for 18 hours. It was then allowed to cool to room temperature and ethanol was removed. The residue was taken up in ethyl acetate (200 ml) and water (50 ml) and the organic layer was washed with water (100 ml×4). The organic layer was dried, filtered, and evaporated to give an oil which was further purified by column chromatography on silica gel (0 to 40% ethyl acetate in hexanes) to give ethyl 2-(3-(3-fluorophenyl)-5-methyl-2-phenyl-1H-pyrrol-1-yl)acetate (1.74 g, 5.16 mmol, 17.87% yield). 1H NMR (CDCl3/400 MHz): δ (ppm) 7.61-7.51 (m, 2H), 7.49-7.40 (m, 3H), 7.40-7.35 (m, 3H), 7.34-7.31 (m, 1H), 6.23 (d, 1H), 4.41 (s, 2H), 4.20 (q, 2H), 2.26 (d, 3H), 1.25 (t, 2H). MS m/z: 338.2 (M+1).

1. customA 250 ml round bottom flask equipped with a stir bar and an addition funnel
2. customThe flask was placed in an oil bath at 35° C
3. additionTo this mixture, was added over the course of 2 hours
4. stirringThe mixture was stirred at 35° C. overnight
5. customThe mixture was quenched with water (100 ml×2)
6. extractionextracted with ethyl acetate (200 ml)
7. washThe organic layer was washed with water (100 ml×3) and brine (100 ml)
8. customThe combined organic layers were dried
9. filtrationfiltered
10. customevaporated
11. customto give an oil
12. temperaturethe resulting mixture was heated at 100° C. for 18 hours
13. temperatureto cool to room temperature
14. customethanol was removed
15. washwater (50 ml) and the organic layer was washed with water (100 ml×4)
16. customThe organic layer was dried
17. filtrationfiltered
18. customevaporated
19. customto give an oil which
20. customwas further purified by column chromatography on silica gel (0 to 40% ethyl acetate in hexanes)

ORD-Eintrag

ord-5ea3d652611a4a3b8d7397f7a219d7dd

Quelldatensatz

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08674115B2