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

Temperature

60 °C

To (S)-2-amino-3-methylbutanoic acid (57 g, 487 mmol) dissolved in dioxane (277 mL) was added a 2 N aqueous sodium hydroxide solution (803 mL, 1606 mmol) followed by the dropwise addition of methyl chloroformate (75 mL, 973 mmol) over 1 hour which caused warming of the solution to occur. After the addition, the mixture was heated at 60° C. for 22 hours, then cooled and extracted with dichloromethane (400 mL). The resultant aqueous layer was cooled in an ice bath, and then 12 N hydrochloric acid was added dropwise until the pH was 2. The resultant mixture was stirred at 0° C. for 2 hours, and then the resultant solid was collected by vacuum filtration, and dried in a vacuum oven to provide 80 g (94%) of the title compound as a colorless solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.50 (bs, 1H), 7.34 (d, J=8.6 Hz, 1H), 3.84 (dd, J=8.6, 6.0 Hz, 1H), 3.54 (s, 3H), 2.03 (m, 1H), 0.86 (t, J=7.0 Hz, 6H).

1. temperaturecaused warming of the solution
2. additionAfter the addition
3. temperaturecooled
4. extractionextracted with dichloromethane (400 mL)
5. temperatureThe resultant aqueous layer was cooled in an ice bath
6. addition12 N hydrochloric acid was added dropwise until the pH was 2
7. filtrationthe resultant solid was collected by vacuum filtration
8. customdried in a vacuum oven

ORD record

ord-a3f8c9a3e6b845ef809a463fac2b17ef

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08921514B2