反应详情

温度

0 °C

Put 1.0 g (11.1 mmol) (3R)-butane-1,3-diol in 20 ml THF at 0° C. Add dropwise 5.55 ml (11.1 mmol) of a 2 M solution of the phosphazene base P2-tert.-butyl in THF and stir for 30 min at 0° C. Then add 2.27 g (11.65 mmol) tert.-butyl bromoacetate. Stir for 30 min at 0° C., then leave to return to RT and stir for a further 1 h. Then dilute with ethyl acetate, add water and acidify with 10% citric acid solution. Extract once more with ethyl acetate, combine the organic phases, wash once with satd. sodium chloride solution, dry over magnesium sulphate and concentrate by evaporation. Purify by chromatography on silica gel (solvent: cyclohexane/ethyl acetate 8:2). 730 mg (32.2% of theor.) of the target compound is obtained, which according to 1H-NMR (doublet at 1.18 ppm) contains approx. 10% of the regioisomer [(1R)-3-hydroxy-1-methylpropyl]oxy}acetic acid tert.-butyl ester.

1. customat 0° C
2. stirringStir for 30 min at 0° C.
3. customleave
4. customto return to RT
5. stirringstir for a further 1 h
6. extractionExtract once more with ethyl acetate
7. washwash once with satd
8. dry with materialsodium chloride solution, dry over magnesium sulphate
9. concentrationconcentrate by evaporation
10. customPurify by chromatography on silica gel (solvent: cyclohexane/ethyl acetate 8:2)
11. custom730 mg (32.2% of theor.) of the target compound is obtained