Hydrochloric Acid → (S)-3-Amino-2-hydroxy-4-methyl-pentanoic acid

Temperature

110 °C

To a solution of ((S)-2-Cyano-2-hydroxy-1-isopropyl-ethyl)-carbamic acid benzyl ester (10) (5.1 g, 19.5 mmol) in 1,4-dioxane (90 mL) was added conc. HCl (90 mL) and anisole (1.5 equiv.) and the mixture was heated to 110° C. for 18 h. The reaction mixture was cooled to ambient temperature and concentrated under vacuum to remove the dioxane. The mixture was then washed with EtOAc and the residue further concentrated under vacuum at 40° C. to remove the conc HCl. Any residual water was removed by azeotroping with toluene. The residue was washed with Et2O (2×50 mL) to afford hydroxyl acid (11) as a gummy solid (crude, mixture of diastereoisomers). 1H NMR (400 MHz, DMSO-d6): δ 8.20 (1H, brs), 7.96 (1H, brs), 4.42 (1H, d J=3.0 Hz), 4.17 (1H, d J=4.0 Hz), 3.17-3.05 (2H, m), 1.98-1.86 (2H, m), 0.96-0.86 (6H, m); m/z 148 (MH)+.

1. temperatureThe reaction mixture was cooled to ambient temperature
2. concentrationconcentrated under vacuum
3. customto remove the dioxane
4. washThe mixture was then washed with EtOAc
5. concentrationthe residue further concentrated under vacuum at 40° C.
6. customto remove the conc HCl
7. customAny residual water was removed
8. customby azeotroping with toluene
9. washThe residue was washed with Et2O (2×50 mL)
10. customto afford
11. additionhydroxyl acid (11) as a gummy solid (crude, mixture of diastereoisomers)

ORD record

ord-a250083123054c059d977601df239b1a

Source dataset

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08541363B2