1,1'-Carbonyldiimidazole → (S)-2-(Boc-Amino)-N-methoxy-n-methylbutyramide

To a solution of (2S)-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)butanoic acid (2.50 g, 12.3 mmol) in THF (15.0 mL) was added 1,1′-carbonyldiimidazole (2.39 g, 14.8 mmol) portionwise over about 10 min. After stirring 30 min at RT, a solution of N,O-dimethylhydroxylamine hydrochloride (1.32 g, 13.5 mmol) and DIPEA (2.36 mL, 13.5 mmol) in DMF (4.0 mL) was added. The reaction mixture was stirred for 2 h at RT, followed by concentration in vacuo. The residue was diluted with EtOAc (50 mL) and washed with 1 M aq. HCl (2×20 mL), saturated aq. NaHCO3 (2×20 mL), and brine (20 mL). The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo to afford the title compound (2.60 g, 88%) as a clear, colorless oil. LC-MS m/z 247 (M+H)+, 0.94 min (ret time).

1. stirringThe reaction mixture was stirred for 2 h at RT
2. concentrationfollowed by concentration in vacuo
3. additionThe residue was diluted with EtOAc (50 mL)
4. washwashed with 1 M aq. HCl (2×20 mL), saturated aq. NaHCO3 (2×20 mL), and brine (20 mL)
5. dry with materialThe organic layer was dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo

ORD record

ord-6e103b332bf44dbf99e5593ed17a04a1

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08841463B2