Diisopropylethylamine → (R)-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 (R)-2-amino-4-methyl-hexanoic acid ethyl ester hydrochloride salt (1.57 g, 7.50 mmol) in acetonitrile (9 mL) was treated with N,N-diisopropylethylamine (1.62 mL) and stirred at 60° C. for 15 min. At this time the solution was treated with N,N-diisopropylethylamine (1.62 mL) and a solution of (E)-4-bromo-3-(2-chloro-phenoxy)-but-2-enoic acid ethyl ester (prepared as in Example 61, 2.39 g, 7.49 mmol) in acetonitrile (4 mL) via a dropping funnel and refluxed for 20 h. The mixture was concentrated in vacuo and the residue partitioned between ethyl acetate and water. The layers were separated and the organic layer was dried over anhydrous sodium sulfate. The mixture was filtered and concentrated in vacuo and the residue dissolved in tetrahydrofuran (8 mL) and transferred to an Emrys Optimizer microwave tube and microwaved at 160° C. for 4 h. The mixture was cooled and concentrated in vacuo and the residue was purified by ISCO flash chromatography (RediSep silica 80 g, 20% to 80% ethyl acetate/hexanes) which afforded (R)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-hexanoic acid ethyl ester (1.26 g, 46%).

Provenance & Evidence