反应详情

To a stirred solution of (2R)-2-amino-3,3-dimethylbutyric acid (5.0 g, 38.12 mmol) in 80 mL of 1N sulfuric acid at −10° C. was dropped in slowly a solution of sodium nitrite (5.26 g, 76.23 mmol) dissolved in 25 mL of water. After addition, the reaction was allowed to slowly equilibrate to ambient temperature over 20 h. Sodium chloride (10 g) was added and the solution was extracted twice with 100 mL portions of diethyl ether. The organic layers were separated, combined, dried over anhydrous sodium sulfate, and filtered. The filtrate solvent was removed under reduced pressure. The residue was purified by preprative HPLC using a chiralpak AD column (5 cm×50 cm) using 5% ethanol in 95% hexanes with 0.2% TFA as the mobile phase at a flow rate of 80 mL/min. The product-containing fractions were concentrated in vacuo. (2R)-3,3-Dimethyl-2-hydroxybutyric acid was obtained as an oil that crystallizes on sitting (2.2 g; 44%).

1. additionAfter addition
2. customslowly equilibrate to ambient temperature
3. customover 20 h
4. extractionthe solution was extracted twice with 100 mL portions of diethyl ether
5. customThe organic layers were separated
6. dry with materialdried over anhydrous sodium sulfate
7. filtrationfiltered
8. customThe filtrate solvent was removed under reduced pressure
9. customThe residue was purified by preprative HPLC
10. concentrationThe product-containing fractions were concentrated in vacuo