2-Fluoro-5-nitroaniline → HCID 4124756, compound

Participants

Reaction Steps

2-Fluoro-5-nitroaniline (500 mg, 3.2 mmol) and diisopropylethylamine (1.1 ml, 6.4 mmol) were stirred in dry dichloromethane (10 ml) under nitrogen. 4-Chlorobutyryl chloride was added drop-wise over 1 minute and the reaction was stirred for a further 2 hrs. The reaction mixture was partitioned between water (50 ml) and dichloromethane (50 ml). The organics were collected, dried (magnesium sulphate), concentrated in vacuo and the residue purified by flash column chromatography (SiO2) eluting with dichloromethane to give 537 mg of 4-chloro-N-(2-fluoro-5-nitro-phenyl)-butyramide as a white solid. This material was re-dissolved in dry tetrahydrofuran and cooled over an ice-bath. Sodium hydride (83 mg, 2 mmol) was added and the reaction was stirred at room temperature for 3 hr. The reaction mixture was concentrated in vacuo and the residue was dissolved in dichloromethane (50 ml). The organics were washed with water (50 ml), dried (magnesium sulphate) and concentrated in vacuo to give 430 mg of crude 1-(2-fluoro-5-nitro-phenyl)-pyrrolidin-2-one as a yellow solid. This material was suspended in diethyl ether (20 ml) and ethanol (2 ml). A solution of tin (II) chloride dihydrate in concentrated HCl (20 ml) was added drop-wise over 5 minutes and the reaction stirred at room temperature for 3 hrs. The reaction mixture was neutralised to pH 7 by addition of 2M sodium hydroxide (aq) and the resulting solution was extracted with dichloromethane (2×100 ml). The organic extracts were combined, dried (magnesium sulphate) and concentrated in vacuo to afford crude 1-(5-amino-2-fluoro-phenyl)-pyrrolidin-2-one (424 mg, 68%) as a yellow solid. HPLC retention time 3.3 min. Mass spectrum (ES+) m/z 195 (M+H).

Provenance & Evidence