Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1) → 4-(4-fluorophenyl)-7-[({5-[1-hydroxy-1-(trifluoromethyl)propyl]-1,3,4-oxadiazol-2-yl}amino)methyl]-2H-chromen-2-one

Participants

Reaction Steps

A mixture of oxadiazole (14.41 g, 68.2 mmol) of step 3 and 4-(4-fluorophenyl)-2-oxo-2H-chromene-7-carbaldehyde (14.1 g, 52.5 mmol) in toluene (160 mL) with 10% of PPTS was brought to reflux and let go overnight. The system was equipped with a Dean-Stark trap to collect water. The solvent was removed and the crude oil (1H NMR (400 MHz, acetone-d6): δ 9.33 (1H, s, imine)) obtained was diluted in EtOH (ca. 75 mL) at 0° C. To this solution was added NaBH4 (1.9 g) portionwise and the reaction was quenched with a solution of NH4Cl after 45 min. The mixture was saturated with NaCl and extracted with EtOAc (3×200 mL). The organic phases were combined and dried over MgSO4. Purification over silica gel chromatography using toluene-EtOAc (55:45) gave the title compound. 1H NMR (400 MHz, acetone-d6): δ 7.65 (m, 2H), 7.50 (m, 3H), 7.38 (m, 3H), 6.35 (s, 1H), 6.06 (s, 1H), 4.70 (m, 2H), 2.21 (m, 1H), 2.11 (m, 1H) and 0.98 (t, 3H).

Provenance & Evidence