Toluene → N-((5-bromopyridin-3-yl)methyl)ethanesulfonamide

Temperature

120 °C

A flask is charged with 5-bromonicotinaldehyde (1.15 g, 6.18 mmol), ethanesulfonamide (1.35 g, 12.37 mmol) and toluene (120 mL), and titanium isopropoxide (2.64 g, 9.27 mmol) is added dropwise. The mixture is stirred at 120° C. overnight. The mixture is concentrated in vacuo. The residue is taken up in DCM (100 mL) and MeOH (100 mL) and NaBH4 (0.468 g, 12.37 mmol) is added at 0° C. The mixture is stirred at 0° C. for 30 min. Water (50 mL) is then added and the mixture is stirred for 5 min. The suspension is filtered through a pad of celite. The celite layer is washed with DCM (50 mL×3). The filtrate is concentrated in vacuo. The resulting aqueous phase is extracted with DCM (500 mL) and the organic phase is dried over Na2SO4, silica gel (20 g) added, and concentrated in vacuo. The residue is purified by silica chromatography eluting with a 0 to 7% MeOH-DCM gradient to give N-((5-bromopyridin-3-yl)methyl)ethanesulfonamide. MS (ESI) m/z 278.9, 280.8, (M+H)+.

1. additionis added dropwise
2. concentrationThe mixture is concentrated in vacuo
3. stirringThe mixture is stirred at 0° C. for 30 min
4. stirringthe mixture is stirred for 5 min
5. filtrationThe suspension is filtered through a pad of celite
6. washThe celite layer is washed with DCM (50 mL×3)
7. concentrationThe filtrate is concentrated in vacuo
8. extractionThe resulting aqueous phase is extracted with DCM (500 mL)
9. dry with materialthe organic phase is dried over Na2SO4, silica gel (20 g)
10. additionadded
11. concentrationconcentrated in vacuo
12. customThe residue is purified by silica chromatography
13. washeluting with a 0 to 7% MeOH-DCM gradient

ORD record

ord-7c9f3b52f73f43c4a9e843c688ed82fa

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09242963B2