Pyridine → 5-(N-isobutyloxycarbonyl-1,4-dihydro-4-pyridyl)-6-(4-fluoro-phenyl)-2,3-dihydroimidazo[2,1-b]thiazole

Participants

Reaction Steps

6-(4-Fluorophenyl)-2,3-dihydroimidazo[2,1-b]-thiazole (10.0 g, 0.0456 mol) and 11 mol (0.136 mol) of pyridine (previously stirred over potassium hydroxide) were dissolved in 150 ml of methylene chloride. To this cooled solution (10°) was added 17.75 g (0.13 mol) of isobutylchloroformate in 20 ml of methylene chloride under a nitrogen atmosphere. During the addition, the reaction pot temperature was not allowed to rise past 10°. After the addition, the reddish-colored solution was stirred at ambient temperature for 1 hour then heated under reflux for an additional 15 minutes. Thin-layer chromatography (ethyl acetate/hexane/methanol, 15:1:0.1) detected the presence of starting material. An additional 2.13 g (27 mmol) of pyridine, followed by 3.67 g (27 mmol) of isobutyl chloroformate, was added to the reaction vessel. The solution was stirred at room temperature for 1 hour, then, heated to reflux for 15 minutes. Thin layer analysis at this time did not detect starting material. The reaction mixture was diluted with 200 ml of water and extracted with methylene chloride (3×100 ml). The organic layer was dried, then, concentrated to yield 16.0 (85%) of 5-(N-isobutyloxycarbonyl-1,4-dihydro-4-pyridyl)-6-(4-fluoro-phenyl)-2,3-dihydroimidazo[2,1-b]thiazole; m.p. 144°-146° (from acetone/hexane).

Provenance & Evidence