Sulfuric Acid → Isopropyltriphenylphosphonium iodide

Participants

Reaction Conditions

Reaction Steps

Cyclopropanation of 3-methoxy-cinnamic acid methyl ester was carried out following the procedure of Ahmand et al., J Med. Chem 2001, 44, 3302-3310. Isopropyl-triphenylphosphonium iodide was prepared as described by Grieco et al., Tet. Lett. 1972, 36, 3781-3783. Briefly, a solution of 3-methoxy-cinnamic acid ethyl ester (14.6 g, 70.9 mmol) in 300 mL THF was cooled in a dry ice/acetone bath to approximately −78° C., and added dropwise to a −78° C. stirring solution of isopropyl-triphenylphosphonium iodide (51 g. 118 mmol) and n-butyl-lithium (54 mL, 135 mmol) in THF. The reaction mixture was allowed to warm to 0° C. with stirring for two hours, then was stirred at room temperature for 15 hours. The reaction mixture was poured onto ice and the resulting aqueous mixture was adjusted to neutral pH by addition of 1M aqueous H2SO4. The aqueous solution was extracted three times with a 1/1 mixture of hexanes/EtOAc and once with EtOAc. The combined organic layers were filtered through silica, and the filtrate was dried over MgSO4, filtered, and concentrated under reduced pressure to give 15.22 g of crude trans-3-(3-methoxy-phenyl)-2,2-dimethyl-cyclopropanecarboxylic acid ethyl ester.

Provenance & Evidence