Acetone → Tert-butyl 6,6-dimethyl-4-oxo-4,6-dihydrofuro[3,4-d]thiazol-2-ylcarbamate

Temperature

-78 °C

To a solution of diisopropylamine (23.5 mL, 165 mmol) in tetrahydrofuran (200 mL) was added butyllithium (103 mL, 1.6 M in hexanes, 165 mmol) dropwise at −78° C. The solution was stirred at −78° C. for 30 minutes then transferred via cannula into a solution of methyl 2-(tert-butoxycarbonylamino)thiazole-4-carboxylate (Combi-Blocks, 14.2 g, 55 mmol) in tetrahydrofuran (300 mL) at −78° C. After stirring at −78° C. for 30 minutes, dry acetone (Acros, 16.2 mL, 220 mmol) was added dropwise and the reaction mixture was allowed to warm to room temperature and stirred overnight. The reaction mixture was quenched with saturated aqueous NH4Cl solution (200 mL) and the aqueous layer was extracted with ethyl acetate (4×200 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated. The residue was purified by column chromatography (SiO2, 0-100% ethyl acetate in hexanes) to afford the title compound MS (ESI+) m/z 285 (M+H)+.

1. stirringAfter stirring at −78° C. for 30 minutes
2. temperatureto warm to room temperature
3. stirringstirred overnight
4. customThe reaction mixture was quenched with saturated aqueous NH4Cl solution (200 mL)
5. extractionthe aqueous layer was extracted with ethyl acetate (4×200 mL)
6. dry with materialThe combined organic extracts were dried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was purified by column chromatography (SiO2, 0-100% ethyl acetate in hexanes)

ORD record

ord-6291e4eb0ec94cc0b227aa2123b0fb8c

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08546583B2