Methyl vinyl ketone → N-benzyl-2-nitro-N-(3-oxobutyl)benzenesulfonamide

To a solution of benzylamine (1 ml, 9.16 mmol) in ethyl acetate (10 ml) was added triethylamine (1.252 ml, 9.16 mmol) followed 2-nitrobenzene-1-sulfonyl chloride (2.03 g, 9.16 mmol) at 5-10° C. with stirring. The mixture was stirred for 1 hour (complete by HPLC), stirring continued for 1 hour. The reaction mixture was quenched with water. The organic layer was separated, washed with brine, dried, and concentrated under reduced pressure. The residue was dissolved in ethyl acetate (8 ml) and to the resulting solution potassium tert-butoxide (0.051 g, 0.458 mmol) was added followed by methyl vinyl ketone (0.755 ml, 9.16 mmol) with stirring in one portion at 20-25° C. The mixture was stirred for 2 hours at 20-25° C., quenched with brine. The organic phase was separated and the aqueous layer was back extracted with ethyl acetate (5 mL). The combined organic layers were washed with 0.6N HCl (10 mL), concentrated to 3 volumes. The solution was diluted with isopropanol (20 mL), concentrated under reduced pressure until a precipitate appeared. The resulting slurry was then stirred at 20° C. for 4 hours, filtered. The collected solid was then washed with 2-propanol (2×40 mL), dried to give N-benzyl-2-nitro-N-(3-oxobutyl)benzenesulfonamide (2.5 g, 6.87 mmol, 75% yield).

1. customat 5-10° C.
2. stirringThe mixture was stirred for 1 hour (complete by HPLC)
3. stirringstirring
4. customThe reaction mixture was quenched with water
5. customThe organic layer was separated
6. washwashed with brine
7. customdried
8. concentrationconcentrated under reduced pressure
9. additionwas added
10. stirringwith stirring in one portion at 20-25° C
11. stirringThe mixture was stirred for 2 hours at 20-25° C.
12. customquenched with brine
13. customThe organic phase was separated
14. extractionthe aqueous layer was back extracted with ethyl acetate (5 mL)
15. washThe combined organic layers were washed with 0.6N HCl (10 mL)
16. concentrationconcentrated to 3 volumes
17. additionThe solution was diluted with isopropanol (20 mL)
18. concentrationconcentrated under reduced pressure until a precipitate
19. stirringThe resulting slurry was then stirred at 20° C. for 4 hours
20. filtrationfiltered
21. washThe collected solid was then washed with 2-propanol (2×40 mL)
22. customdried

ORD record

ord-e291c9c8070c460eb5d1d51f2ef3dbfd

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09346751B2