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

Na2CO3 (1.83 g, 17.2 mmol) was added to NaOH (33 mL of 1M/H2O, 33 mmol) solution of L-valine (3.9 g, 33.29 mmol) and the resulting solution was cooled with ice-water bath. Methyl chloroformate (2.8 mL, 36.1 mmol) was added dropwise over 15 min, the cooling bath was removed and the reaction mixture was stirred at ambient temperature for 3.25 hr. The reaction mixture was washed with ether (50 mL, 3×), and the aqueous phase was cooled with ice-water bath and acidified with concentrated HCl to a pH region of 1-2, and extracted with CH2Cl2 (50 mL, 3×). The organic phase was dried (MgSO4) and evaporated in vacuo to afford Cap-51 as a white solid (6 g). 1H NMR for the dominant rotamer (DMSO-d6, δ=2.5 ppm, 500 MHz): 12.54 (s, 1H), 7.33 (d, J=8.6, 1H), 3.84 (dd, J=8.4, 6.0, 1H), 3.54 (s, 3H), 2.03 (m, 1H), 0.87 (m, 6H). HRMS: Anal. Calcd. for [M+H]+ C7H14NO4: 176.0923. found 176.0922.

1. temperaturethe resulting solution was cooled with ice-water bath
2. customthe cooling bath was removed
3. washThe reaction mixture was washed with ether (50 mL, 3×)
4. temperaturethe aqueous phase was cooled with ice-water bath
5. extractionextracted with CH2Cl2 (50 mL, 3×)
6. dry with materialThe organic phase was dried (MgSO4)
7. customevaporated in vacuo

ORD record

ord-9f9d8ae94ecf4bf78b21df0bb55aac90

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09303007B2