1,2-Dichloroethane → (R)-tert-butyl 4-(methoxy(methyl)amino)-4-oxobutan-2-ylcarbamate

To a solution of (R)-3-(tert-butoxycarbonylamino)butanoic acid (4.30 g, 21.16 mmol) in DMF (20 mL) and DCM (20.00 mL) was added EDC (4.46 g, 23.27 mmol) and HOBt (4.21 g, 27.5 mmol). The mixture was stirred at rt for 15 min, then N,O-dimethylhydroxylamine hydrochloride (3.10 g, 31.7 mmol) was added, followed by TEA (5.90 mL, 42.3 mmol) dropwise. The resulting light yellow suspension was stirred at rt for 7 hr. The reaction was quenched with addition of water (100 mL). The mixture was extracted with EtOAc (2×). The combined EtOAc extracts were washed with water (2×), 0.3 M aqueous KHSO4, saturated aqueous NaHCO3 (2×), saturated aqueous NaCl (2×), dried over Na2SO4, filtered and concentrated to give (R)-tert-butyl 4-(methoxy(methyl)amino)-4-oxobutan-2-ylcarbamate (2.48 g, 10.1 mmol, 47.6% yield) as a pale yellow solid. 1H NMR (400 MHz, CDCl3) δ ppm 5.32 (s, 1H), 4.14-3.96 (m, 1H), 3.68 (s, 3H), 3.18 (s, 3H), 2.71 (dd, J=15.6, 4.6 Hz, 1H), 2.61-2.49 (m, 1H), 1.41 (d, J=17.2 Hz, 9H), 1.24 (d, J=6.7 Hz, 3H).

1. stirringThe resulting light yellow suspension was stirred at rt for 7 hr
2. customThe reaction was quenched with addition of water (100 mL)
3. extractionThe mixture was extracted with EtOAc (2×)
4. washThe combined EtOAc extracts were washed with water (2×), 0.3 M aqueous KHSO4, saturated aqueous NaHCO3 (2×), saturated aqueous NaCl (2×)
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated

ORD record

ord-ebea379385cf492a9717238b3f9a369b

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09346852B2