反应详情

温度

0 °C

(±)-2-Hydroxy-3-phenylpropanoic acid (Sigma, 3.0 g, 18 mmol) was dissolved in 13 mL of DMF and chilled to 0° C. Imidazole (2.5 g, 36 mmol) and tert-butyldimethylsilylchloride (10 g, 69 mmol) were added. The mixture was allowed to warm to room temperature. After 12 hours, the mixture was diluted with 450 mL of 1:1 EtOAc:hexanes. The mixture was washed with 300 mL of 1M citric acid, 300 mL of water, and 150 mL of sat. Na2SO4, and the organic layer was evaporated. The residue was taken up in 170 mL of MeOH. The resulting mixture was chilled to 0° C. and potassium carbonate (5.7 g, 42 mmol) and 60 mL of water were added. The mixture was warmed to room temperature and stirred for 4 hours. The solvent was evaporated under reduced pressure. The residue was taken up in 5 mL of water and 1 M citric acid was added until the mixture reached pH 4.0. The mixture was extracted with EtOAc (3×100 mL), and the combined organic extracts were dried over MgSO4. The mixture was filtered and evaporated under reduced pressure. The residue was purified by flash chromatography on silica gel (eluting with a gradient of 10% to 30% EtOAc in hexanes) to afford (±)-2-(tert-butyldimethylsilyloxy)-3-phenylpropanoic acid (2.0 g, 40%) as a clear oil. 1H NMR (400 MHz, CDCl3): ppm 7.49-7.37 (m, 5H), 4.60 (dd, J=3.7 Hz, 7.6 Hz, 1H), 3.30 (dd, J=3.7 Hz, 13.7 Hz, 1H), 3.12 (dd, J=7.8 Hz, 13.6 Hz, 1H), 1.03 (s, 9H), 0.12 (s, 3H), 0.00 (s, 3H). Carboxyl H was not detected.

1. temperatureto warm to room temperature
2. washThe mixture was washed with 300 mL of 1M citric acid, 300 mL of water, and 150 mL of sat. Na2SO4
3. customthe organic layer was evaporated
4. temperatureThe resulting mixture was chilled to 0° C.
5. temperatureThe mixture was warmed to room temperature
6. customThe solvent was evaporated under reduced pressure
7. addition1 M citric acid was added until the mixture
8. extractionThe mixture was extracted with EtOAc (3×100 mL)
9. dry with materialthe combined organic extracts were dried over MgSO4
10. filtrationThe mixture was filtered
11. customevaporated under reduced pressure
12. customThe residue was purified by flash chromatography on silica gel (
13. washeluting with a gradient of 10% to 30% EtOAc in hexanes)