反应详情

A mixture of 32.8 g (147 mmol) of methyl (R)-2-pivaloyloxypropionate, 30.5 g (261.8 mmol) of sodium chloroacetate, 26.4 g (261.55 mmol) of triethylamine, and 400 mL of THF was cooled in ice, and 299 g (523.5 mmol) of a 1.75 M solution of tert-butylmagnesium chloride was added dropwise thereto over a period of 3 hours. After the completion of the dropwise addition, the reaction was performed at 25° C. for another 2 hours, and the reaction solution was cooled in ice. A solution of 45 ml of concentrated hydrochloric acid/200 ml of water was added thereto, and subsequently 250 mL of ethyl acetate was added. Furthermore, concentrated hydrochloric acid was added for adjusting the pH to 6.0. Stirring was performed at 25° C. for 1 hour. The resulting ethyl acetate layer was separated, and 150 mL of ethyl acetate was added to the resulting aqueous layer to perform extraction again. The resulting ethyl acetate layers were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 42.6 g of a crude product as an oil. A quantitative analysis was performed by HPLC. Thereby, 29.4 g of the title compound was obtained (yield: 82%, 98.7% e.e.) (HPLC, column: YMC-A302 manufactured by YMC Co. Ltd.; mobile phase: acetonitrile/20 mM (potassium) phosphate buffer solution (pH=2.5)=6/4, flow rate: 1.0 mL/min, column temperature: 30° C., detector: UV 210 nm, retention time: 5 minutes) 1H-NMR (400 MHz, CDCl3) δ: 1.25 (s, 9H), 1.46 (d, 1H, J=6.6 Hz), 4.30 (s, 2H), 5.27 (q, 1H, J=6.6 Hz).

1. temperaturewas cooled in ice
2. additionAfter the completion of the dropwise addition
3. waitthe reaction was performed at 25° C. for another 2 hours
4. temperaturethe reaction solution was cooled in ice
5. waitwas performed at 25° C. for 1 hour
6. customThe resulting ethyl acetate layer was separated
7. addition150 mL of ethyl acetate was added to the resulting aqueous layer
8. extractionextraction again
9. dry with materialdried over anhydrous sodium sulfate
10. concentrationconcentrated under reduced pressure
11. customto obtain 42.6 g of a crude product as an oil