Dimethylformamide → N-(1,1-Dimethylethyl)-1-formylcyclopropanesulfonamide

Temperature

-78 °C

To a round-bottom flask equipped with a stir bar was added N-(tert-butyl)cyclopropanesulfonamide (10.0 g, 56.4 mmol) and THF (220 mL). The flask was placed under a nitrogen atmosphere and the solution was then cooled to −78° C. To the stirred solution was added dropwise over 10 minutes n-butyllithium (46.3 mL, 2.5M in hexanes). The resulting solution was stirred at −78° C. for 30 mins and then the cold bath was removed and the solution was allowed to warm to room temperature temperature with stirring for 30 mins. The solution was cooled to −78° C. To the solution was added N,N-dimethylformamide (13.1 mL, 169 mmol). The solution was allowed to slowly warm to room temperature with stirring for 17 h. The mixture was concentrated and the resulting yellow residue was dissolved in EtOAc (100 mL). The solution was transferred to a separatory funnel and was washed with aq. 1N HCl (150 mL). The aqueous phase was extracted with EtOAc (2×100 mL) and the combined organics were washed with sat. aq. NaCl (50 mL); dried over Na2SO4; and filtered. The filtrate concentrated in vacuo to afford a yellow viscous oil which solidified upon standing at room tempearture. This material was dissolved in EtOAc (10 mL); diluted with hexanes (50 mL); and the resulting solution was then stored at −78° C. for 2 h upon which crystals formed. The crystals were collected via filtration; were washed with cold hexanes; and residual solvent was removed in vacuo to afford N-(tert-butyl)-1-formylcyclopropane-1-sulfonamide as a colorless, crystalline solid (8.89 g, 77%). 1H NMR (500 MHz, CDCl3) δ 9.52 (s, 1H), 4.72 (br. s., 1H), 1.90-1.85 (m, 2H), 1.66-1.62 (m, 2H), 1.36 (s, 9H).

1. customTo a round-bottom flask equipped with a stir bar
2. customthe cold bath was removed
3. temperatureto warm to room temperature temperature
4. stirringwith stirring for 30 mins
5. temperatureThe solution was cooled to −78° C
6. temperatureto slowly warm to room temperature
7. stirringwith stirring for 17 h
8. concentrationThe mixture was concentrated
9. dissolutionthe resulting yellow residue was dissolved in EtOAc (100 mL)
10. customThe solution was transferred to a separatory funnel
11. washwas washed with aq. 1N HCl (150 mL)
12. extractionThe aqueous phase was extracted with EtOAc (2×100 mL)
13. washthe combined organics were washed with sat. aq. NaCl (50 mL)
14. dry with materialdried over Na2SO4
15. filtrationand filtered
16. concentrationThe filtrate concentrated in vacuo
17. customto afford a yellow viscous oil which
18. waitand the resulting solution was then stored at −78° C. for 2 h upon which crystals
19. customformed
20. filtrationThe crystals were collected via filtration
21. washwere washed with cold hexanes
22. customand residual solvent was removed in vacuo

ORD record

ord-5366639dc7164a2ab5d4ef9af2260069

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08957203B2