1-Methyl-2-imidazolecarboxaldehyde → HCID 54418120, compound

Temperature

-20 °C

A flame dried, N2 purged, 100 ml round bottom flask equipped with a dropping funnel, thermometer and magnetic stirrer was charged with 5-(benzyloxy)-2,3-dihydrobenzofuran-6-yl methyltriphenylphosphonium iodide (3.0 g, 4.8 mmoles) and anhydrous THF (15 ml). The suspension was cooled to -20° C. and a 1.55 M solution of n-butyllithium (3.1 ml, 4.8 mmoles) was added dropwise, while maintaining an internal reaction temperature of -20° C. The suspension became a red solution and stirring was continued 1 hour more at 0° C. The reaction mixture was chilled to -25° C. and a solution of 1-methylimidazole-2-carboxaldehyde (525 mg, 4.8 mmoles) in THF. (10 ml) was added dropwise over 5 minutes. The reaction mixture was allowed to warm to room temperature and stir for 12 hours. It was then cooled to 0° C. and water (1.0 ml) added. It was further stirred for 1/2 hour whereupon the solvent was removed in vacuo to afford the crude product. The crude product was dissolved in ethyl ether (20 ml) and water (20 ml). The layers were partitioned and separated. The organic phase was washed with water (2×20 ml), dried over MgS04, suction filtered, and the filtrate concentated in vacuo to yield a crude yellow oil. Further purification was achieved by high performance liquid chromatography to produce approximately a 1:1 ratio of cis and trans isomers of 1-(5-benzyloxy-2,3-dihydrobenzofuran-6-yl)-2-(1-methyl-imidazol-2-yl)ethene (600 mg, 38%).

1. customA flame dried
2. customN2 purged
3. custom100 ml round bottom flask equipped with a dropping funnel
4. temperaturewhile maintaining an internal reaction temperature of -20° C
5. temperatureThe reaction mixture was chilled to -25° C.
6. addition(10 ml) was added dropwise over 5 minutes
7. temperatureto warm to room temperature
8. stirringstir for 12 hours
9. temperatureIt was then cooled to 0° C.
10. stirringIt was further stirred for 1/2 hour whereupon the solvent
11. customwas removed in vacuo
12. customto afford the crude product
13. customThe layers were partitioned
14. customseparated
15. washThe organic phase was washed with water (2×20 ml)
16. customdried over MgS04, suction
17. filtrationfiltered
18. customto yield a crude yellow oil
19. customFurther purification

ORD record

ord-ee6fb84d57444ea99360749d440b81e1

Source dataset

uspto-grants-1988_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04775679