Lawesson's reagent → tert-butyl ((5-((2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octan-2-yl)-1,3,4-thiadiazol-2-yl)methyl)carbamate

温度

70 °C

Lawesson's reagent (0.68 g, 1.68 mol) was added to a solution of tert-butyl 2-(2-((2S,5R)-6-(benzyloxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)hydrazinyl)-2-oxoethylcarbamate (0.50 g, 1.12 mmol) in THF (30 mL). The reaction mixture was heated at 70° C. for 0.5 h. The solution was cooled down to rt and saturated NaHCO3 was added. The organic layer was separated and the aqueous layer was exacted with EtOAc (2×). The combined organic layer was dried over Na2SO4, and concentrated. The crude sample was dissolved in THF (100 mL), and Hg(OAc)2 (1.68 g) was added. The mixture was stirred at rt overnight, filtered and concentrated. The residue was dissolved in EtOAc (100 mL), stirred for 30 min, filtered and concentrated. The crude material was purified by silica gel column chromatography (20% to 50% EtOAc/petroleum ether) to give tert-butyl ((5-((2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octan-2-yl)-1,3,4-thiadiazol-2-yl)methyl)carbamate (230 mg, 45%) as a white solid. ESI-MS (EI+, m/z): 446.2 [M+H]+.

1. temperatureThe solution was cooled down to rt
2. customThe organic layer was separated
3. dry with materialThe combined organic layer was dried over Na2SO4
4. concentrationconcentrated
5. dissolutionThe crude sample was dissolved in THF (100 mL)
6. additionHg(OAc)2 (1.68 g) was added
7. filtrationfiltered
8. concentrationconcentrated
9. dissolutionThe residue was dissolved in EtOAc (100 mL)
10. stirringstirred for 30 min
11. filtrationfiltered
12. concentrationconcentrated
13. customThe crude material was purified by silica gel column chromatography (20% to 50% EtOAc/petroleum ether)

ORDレコード

ord-7ad57134d7244830934556f4dce1b915

出典データセット

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09108966B2