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, at which time the reaction was complete as determined 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 fitted filtered with silica gel and eluted with 9:1 hexanes:ethyl acetate and then with 1:1 hexane:ethyl acetate to give 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. customa large fitted
9. filtrationfiltered with silica gel
10. washeluted with 9:1 hexanes