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

Temperature

-40 °C

A mixture of 5-bromonicotinaldehyde (372 mg, 2 mmol), ethanesulfonamide (273 mg, 2.500 mmol) and titanium(IV) isopropoxide (1172 μl, 4.00 mmol) in toluene (20 mL) was heated to reflux for 2 h. After concentration, the residue was dissolved in THF (25 mL) and cooled to −40° C. A solution of cyclopropylmagnesium bromide (10 mL, 5.00 mmol) was added dropwise and the resulting mixture was slowly warmed up to −20° C. and stirred at this temperature for 4 h. After quenching by saturated 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 product as oil (430 mg). 1H NMR (400 MHz, CDCl3): δ 0.2-0.3 (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), 3.6-3.7 (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 h
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 quenching by saturated 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-6883335039a94d97957b07e60528073f

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08519142B2