Ethanesulfonamide → N-((5-bromopyridin-3-yl)(cyclopropyl)methyl)ethanesulfonamide

Temperature

-40 °C

A mixture of 5-bromonicotinaldehyde (1.860 g, 10 mmol), ethanesulfonamide (1.091 g, 10.00 mmol) and titanium(IV) isopropoxide (5.86 ml, 20.00 mmol) in Toluene (20 mL) was heated to reflux for 2 hr. After concentration, the residue was dissolved in THF (25 mL) and cooled to −40° C. A solution of cyclopropylmagnesium bromide (50.0 ml, 25.00 mmol) was added dropwise and the resulting mixture was slowly warmed up to −20° C. and stirred at this temperature for 4 hr. After quenched by NH4Cl solution, filtration, extraction with CH2Cl2, the solution was dried over Na2SO4, and concentrated, the residue was purified by flash column (ethyl acetate heptane, v/v, 10%-35%) and yielded the title compound (1.5 g). 1H NMR (400.3 MHz, CDCl3): δ0.2-0.3 (m, 1H), 0.4-0.5 (m, 1H), 0.5-0.6 (m, 1H), 0.6-0.7 (m, 1H), 1.0-1.1 (m, 1H), 1.1-1.2 (m, 3H), 2.55-2.75 (m, 2H), 3.8-3.7 (m, 1H), 4.51 (brd, J=4.8 Hz, 1H), 7.73 (s, 1H), 8.42 (s, 1H), 8.51 (s, 1H).

1. temperaturewas heated
2. temperatureto reflux for 2 hr
3. concentrationAfter concentration
4. dissolutionthe residue was dissolved in THF (25 mL)
5. temperaturethe resulting mixture was slowly warmed up to −20° C.
6. customAfter quenched by NH4Cl solution, filtration, extraction with CH2Cl2
7. dry with materialthe solution was dried over Na2SO4
8. concentrationconcentrated
9. customthe residue was purified by flash column (ethyl acetate heptane, v/v, 10%-35%)

ORD record

ord-80efb1aceace4aa0a9cfe58961e745d5

Source dataset

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08455522B2