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 heated to 115° C. over night 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 and washed with DCM (3×100 mL). The aqueous layer was separated and extracted with DCM (2×200 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. filtrationthe resulting suspension was filtered through a pad of Dicalite
3. washwashed with DCM (3×100 mL)
4. customThe aqueous layer was separated
5. extractionextracted with DCM (2×200 mL)
6. dry with materialCombined organics were dried over Na2SO4
7. filtrationfiltered
8. customThe residue was purified by silica gel flash chromatography
9. washeluting with a 0 to 5% MeOH-DCM gradient

ORD record

ord-b80c662b98924ef9b0498a721721b10e

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09260408B2