Diisopropylethylamine → (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-hexanoic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

A suspension of (S)-2-amino-4-methyl-hexanoic acid ethyl ester hydrochloride salt (1.05 g, 5.01 mmol) in acetonitrile (6 mL) was treated with N,N-diisopropylethylamine (1.0 mL) and stirred at 60° C. for 15 min. To this mixture was added N,N-diisopropylethylamine (1.2 mL) and a solution of (E)-4-bromo-3-(2-chloro-phenoxy)-but-2-enoic acid ethyl ester (prepared in Example 61, 1.6 g, 5.0 mmol) in acetonitrile (4 mL) via a dropping funnel and the resulting mixture refluxed for 20 h. The resulting mixture was concentrated in vacuo and the residue was partitioned between ethyl acetate and water. The layers were separated and the organic layer was dried over sodium sulfate. The mixture was filtered and concentrated in vacuo and the residue dissolved in tetrahydrofuran (8 mL). The resulting solution was transferred to an Emrys Optimizer microwave tube and microwaved at 160° C. for 4 h. The mixture was concentrated in vacuo and the residue purified by ISCO flash chromatography (RediSep silica column 80 g, 20% to 80% ethyl acetate/hexanes) which afforded (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-hexanoic acid ethyl ester (950 mg, 52%).

Provenance & Evidence