Iodine → Ethyl 2-cyclopropyl-2-hydroxyacetate

Participants

Reaction Conditions

Reaction Steps

A flame dried two-neck round bottom flask fitted with a reflux condenser and N2 outlet was charged with anhydrous THF, freshly activated Mg (120 mg, 4.95 mmol) and a catalytic amount of iodine. A small portion of cyclopropyl bromide dissolved in THF was added. After initiation of reflux, the reaction mixture was cooled to −20° C. and the remaining cyclopropyl bromide (500 mg, 4.13 mmol) was gradually added. After 30 min a freshly distilled solution of glyoxylate 45 (549 mg, 5.37 mmol) in THF was added over a 10 min period and the resulting solution was stirred at −20° C. for 2 h before being quenched with a small amount of water. After 10 min the reaction mixture was further diluted with water (50 mL) and extracted with ethyl acetate (3×50 mL). The organic extracts were combined, dried over anhydrous MgSO4, filtered, concentrated in vacuo and purified by column chromatography eluting with ethyl acetate/n-hexane (a gradient of 10-20%) to furnish ethyl α-hydroxycyclopropaneacetate (422 mg, 71%) as a viscous oil. The oil (350 mg, 2.43 mmol) was dissolved in anhydrous DCM and cooled to 0° C. Then Ph3P (2.04 gm, 7.78 mmol) was added followed by CBr4 (1.20 gm, 3.64 mmol). The reaction mixture was stirred at 0° C. for 2 h and then concentrated in vacuo. The Ph3PO was precipitated by addition of n-hexane and removed by filtration. The crude reaction mixture was purified by flash column chromatography to furnish ethyl α-bromocyclopropaneacetate (46, R=c-Pr): (311 mg, 62% yield).

Provenance & Evidence