Reaktion #478487

Reaktionsgleichung

NH4Cl

4-(5-formyl-pyridin-3-yl)-benzonitrile

ethanesulfonamide

toluene

→

N-((5-(4-cyanophenyl)pyridin-3-yl)(cyclopropyl)methyl)ethanesulfonamide

Ausbeute 51.0%

Lösungsmittel

ethyl acetate

brine

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe resulting mixture was heated
2. 2
   Temperaturto reflux for 2 h
3. 3
   EinengenAfter concentration
4. 4
   workup.DISSOLUTIONthe residue was dissolved in THF (10 mL)
5. 5
   workup.ADDITIONwas added dropwise
6. 6
   FiltrationThe mixture was filtered
7. 7
   Sonstigethe organic layer was separated
8. 8
   EinengenAfter concentration
9. 9
   Sonstigethe residue was purified by flash column (MeOH/DCM, v/v, 0-3%)

Vorschrift

Titanium isopropoxide (0.70 mL, 2.40 mmol) was added to a mixture of 4-(5-formyl-pyridin-3-yl)-benzonitrile (250 mg, 1.20 mmol) and ethanesulfonamide (144 mg, 1.32 mmol) in toluene (10 mL) at room temperature. The resulting mixture was heated to reflux for 2 h. After concentration, the residue was dissolved in THF (10 mL) and cooled to −40° C. c-PrMgBr (0.5 M in THF, 12.0 mL, 6.00 mmol) was added dropwise and the resulting mixture was stirred at −36° C. for 1 h. Saturated NH4Cl solution was then added to the reaction mixture. The resulting solution was diluted with ethyl acetate and brine. The mixture was filtered and the organic layer was separated. After concentration, the residue was purified by flash column (MeOH/DCM, v/v, 0-3%) to give N-((5-(4-cyanophenyl)pyridin-3-yl)(cyclopropyl)methyl)ethanesulfonamide (210 mg, 51%); ESI-MS m/z: 342 [M+1]+, 1H-NMR (MeOD, 400 MHz) δ 8.83 (d, J=2.0 Hz, 1H), 8.69 (d, J=2.0 Hz, 1H), 8.24 (t, J=2.0 Hz, 1H), 7.92 (s, 4H), 3.96 (d, J=9.2 Hz, 1H), 3.06-2.93 (m, 2H), 1.35-1.31 (m, 1H), 1.31 (t, J=7.2 Hz, 3H), 0.81-0.76 (m, 1H), 0.67-0.61 (m, 2H), 0.54-0.49 (m, 1H); enantiomers were separated by chiral HPLC (Chiralpak IA-H, EtOH/Heptane, v/v, 70/30) to the first peak (enantiomer 1, t=10.20 min) and the second peak (enantiomer 2, t=15.99 min).

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