L-Valine → (2S)-2-((methoxycarbonyl)amino)-3-methylbutanoic acid

Temperature

0 °C

1N NaOH in water (1250 mL) was added into to L-Valine (150 g, 1280 mmol) in a 3 L round bottom flask equipped with a magnetic stir bar. To this solution was added Na2CO3 (67.8 g, 640 mmol) and the reaction mixture was cooled to 0° C. in an ice-water bath. Methyl chloroformate (107 mL, 1390 mmol) was added dropwise and the reaction mixture was allowed to warm to room temperature. The reaction mixture was stirred for 15 hours. The reaction mixture was washed with ethyl acetate (3×400 mL). The aqueous layer was cooled over an ice-water bath and acidified by concentrated HCl (aq) to pH=2. The reaction mixture was extracted with CH2Cl2 (3×1000 mL). The combined organic layers were dried over Na2SO4 and the solvent was concentrated to afford the crude product. The crude product was heated at reflux with 150 mL ethanol and 150 mL water for 2 hours. Then the mixture was cooled to room temperature and the crystalline solids were filtered to give (S)-2-(methoxycarbonylamino)-3-methyl-butanoic acid (146 g, 65% yield).

1. customequipped with a magnetic stir bar
2. temperatureto warm to room temperature
3. washThe reaction mixture was washed with ethyl acetate (3×400 mL)
4. temperatureThe aqueous layer was cooled over an ice-water bath
5. extractionThe reaction mixture was extracted with CH2Cl2 (3×1000 mL)
6. dry with materialThe combined organic layers were dried over Na2SO4
7. concentrationthe solvent was concentrated
8. customto afford the crude product
9. temperatureThen the mixture was cooled to room temperature
10. filtrationthe crystalline solids were filtered

ORD record

ord-1c144f4865f145faaa9560f79069d7a7

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08815849B2