反应详情

Methyl 2-(4-chlorophenyl)acetate (36.7 g, 199 mmol) and paraformaldehyde (6.27 g, 209 mmol) were dissolved/suspended in DMSO (400 mL) and treated with NaOMe (537 mg, 9.94 mmol). The mixture was allowed to stir at room temperature for 2 hours to completion by TLC analysis of the crude. The reaction was poured into ice-cold water (700 mL; emulsion) and neutralized with the addition of 1M HCl solution. The aqueous layer was extracted with ethyl acetate (3×), and the organics were combined. The organic layer was washed with water (2×), brine (1×), separated, dried over MgSO4, filtered, and concentrated in vacuo to afford the crude product as an oil. The residue was loaded onto a large fritted filtered with silica gel and eluted with 9:1 hexanes:ethyl acetate until the starting material/olefin were collected. The plug was then eluted with 1:1 hexanes:ethyl acetate until the pure desired product was eluted completely. The concentrated pure fractions yielded methyl 2-(4-chlorophenyl)-3-hydroxypropanoate as an oil (39.4 g, 92%).

1. extractionThe aqueous layer was extracted with ethyl acetate (3×)
2. washThe organic layer was washed with water (2×), brine (1×)
3. customseparated
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customto afford the crude product as an oil
8. washeluted with 9:1 hexanes
9. customethyl acetate until the starting material/olefin were collected
10. washThe plug was then eluted with 1:1 hexanes
11. washethyl acetate until the pure desired product was eluted completely