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

Temperature

115 °C

A flask was charged with 5-bromonicotinaldehyde (2.55 g, 13.7 mmol), ethanesulfonamide (2.99 g, 27.4 mmol) and toluene (250 mL), then titanium isopropoxide (5.84 g, 20.6 mmol) was added dropwise. The reaction mixture was stirred at 115° C. overnight and then concentrated in vacuo. The residue was taken up in DCM (200 mL) and MeOH (200 mL) and NaBH4 (1.04 g, 27.4 mmol) was added portionwise at 0° C. The reaction mixture was stirred at 0° C. for 30 min and then poured into water (100 mL) and the resulting suspension was filtered through a pad of dicalite. The dicalite layer was washed with DCM (3×100 mL). The resulting aqueous layer was separated and extracted with DCM (500 mL). Combined organics were dried over Na2SO4, filtered and preadsorbed on silica gel. The residue was purified by silica gel flash chromatography eluting with a 0 to 5% MeOH-DCM gradient to give the title compound (3.01 g, 79%) as an orange solid. MS: 279.0, 281.0 (M+H+).

1. concentrationconcentrated in vacuo
2. stirringThe reaction mixture was stirred at 0° C. for 30 min
3. filtrationthe resulting suspension was filtered through a pad of dicalite
4. washThe dicalite layer was washed with DCM (3×100 mL)
5. customThe resulting aqueous layer was separated
6. extractionextracted with DCM (500 mL)
7. dry with materialCombined organics were dried over Na2SO4
8. filtrationfiltered
9. customThe residue was purified by silica gel flash chromatography
10. washeluting with a 0 to 5% MeOH-DCM gradient

ORD record

ord-4dcbb5994bed46e998b244f58a225bbc

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09133158B2