Sulfur Dioxide → N-[[3-(1,3-dioxolan-2-yl)-2-thienyl]sulfonyl]glycine ethyl ester

To a solution of thiophene-3-carboxaldehyde ethylene acetal (13.27 g, 85.1 mmol) in anhydrous THF (200 mL) at -70° C. was added n-butyllithium (2.5M, 37.4 mL, 93.6 mmol). The solution was stirred for 50 min; a white precipitate formed. Sulfur dioxide was passed through the solution for about 5 min and the mixture was warmed to ambient temperature. The volatiles were evaporated and the residue suspended in methylene chloride (200 mL); this mixture was cooled (0° C.) and N-chlorosuccinimide (14.77 g, 110.6 mmol) added. After stirring at ambient temperature for 3 h the mixture was filtered. The filter pad was washed with ethyl acetate (300 mL) and the combined filtrates were cooled (ice bath) and mixed with a saturated aqueous solution of sodium bicarbonate (250 mL) and glycine ethyl ester hydrochloride (33.99 g, 221 mmol). The mixture was stirred at ambient temperature for 16 h and the organic layer was separated, dried (MgSO4), and evaporated to a residue which was purified by column chromatography (silica, 40% ethyl acetate in hexane) to give a colorless liquid (16.55 g, 61%).

1. customa white precipitate formed
2. customThe volatiles were evaporated
3. additionadded
4. stirringAfter stirring at ambient temperature for 3 h the mixture
5. filtrationwas filtered
6. washThe filter pad was washed with ethyl acetate (300 mL)
7. temperaturethe combined filtrates were cooled (ice bath)
8. stirringThe mixture was stirred at ambient temperature for 16 h
9. customthe organic layer was separated
10. dry with materialdried (MgSO4)
11. customevaporated to a residue which
12. customwas purified by column chromatography (silica, 40% ethyl acetate in hexane)

ORD record

ord-0e57c4e8413c429cba408b2b062eea20

Source dataset

uspto-grants-1997_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05681834