Isopropyl iodide → 8-Oxo-2,2,5-trimethyl-7alpha-isopropyl-3-oxa-1-azabicyclo[4.2.0]octane

Participants

Reaction Conditions

Reaction Steps

THF, 20 ml, is placed under N2, treated with 1.54 ml diisopropylamine and cooled to -78° C. A solution of n-butyl lithium, 1.97 M in hexane (5.6 ml) is added dropwise over 5 min. The reaction mixture is stirred at -78° C. for 10 min and then treated with 8-oxo-2,2,5-trimethyl-3-oxa-1-azabicyclo[4.2.0]octane (1.55 g) in 15 ml THF which is added dropwise over 5 min. After another 10 min hexamethylphosphoramide (1.97 ml) is added. The mixture is stirred another 10 min, then treated with 2 ml of isopropyl iodide. The reaction mixture is stirred at -78° C. for 15 min and allowed to warm to 25° C. and stirred for 15 min. The reaction mixture is diluted with EtOAc, washed once with pH 7 phosphate buffer then dried and evaporated. The residue is chromatographed on silica gel using 25% EtOAc/C6H6 as eluant to give 8-oxo-2,2,5-trimethyl-7α-isopropyl-3-oxa-1-azabicyclo[4.2.0]octane.

Provenance & Evidence