Sodium Bicarbonate → HCID 11264737, compound

Temperature

0 °C

(R)-methyl 2-amino-3-methylbutanoate hydrochloride (4.0 g, 23.86 mmol) was dissolved in THF (60 mL) and methanol (15 mL). The colorless solution was chilled to 0° C., followed by the addition of sodium bicarbonate (6.01 g, 71.6 mmol) in one portion, immediately followed by addition of solid BOC-anhydride (7.81 g, 35.8 mmol). The reaction mixture was allowed to warm to ambient temperature and left stirring overnight, quenched with 200 mL water, and extracted twice with 200 mL MTBE. The organic phase was washed with 200 mL saturated NaHCO3 solution and 200 mL brine, dried over Na2SO4, filtered, and concentrated. The residue was chromatographed on a Grace Reveleris 120 g column, eluted with 0-30% EtOAc in Hexanes (35 mL/min) to obtain the title compound (5.265 g, 22.76 mmol, 95% yield) as a colorless oil. MS (DCI+) m/z 249.2 (M+NH4); 1H NMR (300 MHz, DMSO-d6) δ 7.15 (d, J=8.1, 1H), 3.83 (dd, J=8.0, 6.8, 1H), 3.62 (s, 3H), 2.06-1.91 (m, 1H), 1.38 (s, 9H), 0.86 (dd, J=6.8, 3.2, 6H).

1. temperatureto warm to ambient temperature
2. waitleft
3. customquenched with 200 mL water
4. extractionextracted twice with 200 mL MTBE
5. washThe organic phase was washed with 200 mL saturated NaHCO3 solution and 200 mL brine
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was chromatographed on a Grace Reveleris 120 g column
10. washeluted with 0-30% EtOAc in Hexanes (35 mL/min)

ORD record

ord-c84bb08bcd9642a4b51c51135833df21

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09012651B2