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-840037554aa04caea79c184ade8e78db

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08841334B2