Pyrrolidine → HCID 136463725, compound

Participants

Reaction Steps

A solution of 2-(5-chloro-4-fluoro-2-hydroxybenzoyl)-3-(1,3-dioxolan-2-yl)pyridine (1.45 g), O-t-butylhydroxylamine hydrochloride (1.69 g) and pyrrolidine (9.56 g) in n-propanol (20 ml) was heated for 1.5 hour under reflux. The reaction mixture was concentrated, to which was added water, followed by extraction with ethyl acetate. The extract solution was washed with a saturated aqueous saline solution, dried (anhydrous sodium sulfate), and concentrated. The concentrate was purified by means of a silica gel column chromatography (eluent: ethyl acetate/hexane) to give a mixture (540 mg) of (Z)-2-(5-chloro-4-fluoro-2-hydroxybenzoyl)-3-(1,3-dioxolan-2-yl)pyridine O-t-butyloxime and (Z)-2-[5-chloro-2-hydroxy-4-(pyrrolidin-1-yl)benzoyl]-3-(1,3-dioxolan-2-yl)pyridine O-t-butyloxime (about 2:1). A mixture of this mixture (470 mg), p-toluenesulfonic acid monohydrate (162 mg), acetone (9.0 ml) and water (3.5 ml) was heated for 14 hours under reflux. The reaction mixture was concentrated, to which was added water, followed by extraction with ethyl acetate. The extract solution was washed with a saturated aqueous saline solution, dried (anhydrous sodium sulfate), and concentrated to leave an oily substance. This oily substance was dissolved in chloroform (2.0 ml), to which was added, at room temperature, 50% m-chloroperbenzoic acid (75 mg). The mixture was stirred for 8 minutes at the same temperature, which was then poured into an aqueous solution of sodium sulfite, followed by extraction with ethyl acetate. The extract solution was washed with a saturated aqueous saline solution, dried (anhydrous sodium sulfate), and concentrated. The concentrate was purified by means of a silica gel column chromatography (eluent: ethyl acetate/hexane) to give (Z)-2-(5-chloro-4-fluoro-2-hydroxybenzoyl)-3-formylpyridine O-t-butyloxime (230 mg) (Compound 155).

Provenance & Evidence