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

Temperature

-40 °C

A mixture of 5-bromonicotinaldehyde (930 mg, 5 mmol), ethanesulfonamide (546 mg, 5.00 mmol) and titanium(IV) isopropoxide (2930 μl, 10.00 mmol) in toluene (20 mL) was heated to reflux for 4 h. After concentration, the residue was dissolved in THF (25 mL) and cooled to −40° C. A solution of cyclopentylmagnesium bromide (2M in THF, 6.25 mL, 12.5 mmol) was added dropwise and the resulting mixture was slowly warmed up to 0° C. over 4 h. The reaction was quenched with a saturated NH4Cl solution. The mixture was filtered, separated, and extracted with CH2Cl2. The organic phase was dried over Na2SO4, filtered and concentrated, and the residue was purified by flash column (ethyl acetate/heptane, v/v, 10%-30%) to give a yellow oil (480 mg). ESI-MS m/z: 348.9 [M+1]+; 1H NMR (400 MHz, CDCl3): δ 1.13-1.80 (m, 7H), 1.26 (t, J=7.4 Hz, 3H), 1.97-2.05 (m, 1H), 2.20-2.29 (m, 1H), 2.67-2.92 (m, 2H), 4.27 (t, J=8.8 Hz, 1H), 5.59 (brs, 1H), 7.87 (s, 1H), 8.56 (s, 1H), 8.68 (s, 1H).

1. temperaturewas heated
2. temperatureto reflux for 4 h
3. concentrationAfter concentration
4. dissolutionthe residue was dissolved in THF (25 mL)
5. temperaturethe resulting mixture was slowly warmed up to 0° C. over 4 h
6. customThe reaction was quenched with a saturated NH4Cl solution
7. filtrationThe mixture was filtered
8. customseparated
9. extractionextracted with CH2Cl2
10. dry with materialThe organic phase was dried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated
13. customthe residue was purified by flash column (ethyl acetate/heptane, v/v, 10%-30%)

ORD record

ord-d7e825ed9935430398831b25d3039397

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08519142B2