Hydrochloric Acid → Benzyl {2-[methoxy(methyl)amino]-1,1-dimethyl-2-oxoethyl}carbamate

Temperature

0 °C

N-Methylmorpholine (682 mg, 741 μL, 6.74 mmol) and isobutylchloroformate (460 mg, 441 μL, 3.37 mmol) were added successively to a stirred solution of N-carbobenzyloxy-2-methylalanine (0.64 g, 2.69 mmol) in dry CH2Cl2 at 0° C. under N2. The resulting cloudy mixture was stirred at 0° C. for 90 min. N,O-Dimethylhydroxylamine hydrochloride (316 mg, 3.24 mmol) was added portionwise and the mixture was warmed to room temperature and stirred for 3 h. The mixture was poured into 1N HCl (30 mL) and extracted with CH2Cl2 (3×40 mL). The combined extracts were washed with 1N HCl (30 mL), dried (Na2SO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Si, 40×160 mm, 0-80% EtOAc in hexanes gradient) to afford benzyl {2-[methoxy(methyl)amino]-1,1-dimethyl-2-oxoethyl}carbamate. Rf=0.47 (50% EtOAc in hexanes). LCMS calc.=303.1; found=303.2 (M+Na)+. 1H NMR (500 MHz, CDCl3) δ 7.37-7.29 (m, 5H), 5.82 (s, 1H), 5.09 (s, 2H), 3.60 (s, 3H), 3.18 (s, 3H), 1.60 (s, 6H).

1. temperaturethe mixture was warmed to room temperature
2. stirringstirred for 3 h
3. extractionextracted with CH2Cl2 (3×40 mL)
4. washThe combined extracts were washed with 1N HCl (30 mL)
5. dry with materialdried (Na2SO4)
6. concentrationconcentrated in vacuo
7. customto give the crude product
8. customThis was purified by flash chromatography (Si, 40×160 mm, 0-80% EtOAc in hexanes gradient)

ORD record

ord-a1aff99003374262b6d4df7181fc176f

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08440702B2