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 h. 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 h. After quenching with a NH4Cl solution, filtration and extraction with CH2Cl2, the solution was dried over Na2SO4, filtered and concentrated to give a residue which was purified by flash column (ethyl acetate/heptane, v/v, 10%-35%) to yield the title compound (1.5 g). 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 with a NH4Cl solution, filtration and extraction with CH2Cl2
7. dry with materialthe solution was dried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated
10. customto give a residue which
11. customwas purified by flash column (ethyl acetate/heptane, v/v, 10%-35%)

ORD record

ord-622483cd973949afb12a7ecac259321a

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08519142B2