Tetrahydrofuran → HCID 68957797, compound

Participants

Reaction Conditions

Reaction Steps

An oven-dried 1 L three-neck flask equipped with magnetic stir bar, nitrogen gas inlet valve, and digital thermometer probe, and addition funnel had been charged with 1-[4-(tert-butyl-dimethyl-silanyloxy)-phenyl]-2-phenyl-ethanone oxime (Compound B, 26.6 g) and anhydrous THF (140 mL.) The reaction vessel is submerged in an ice-methanol bath equipped with a thermometer reading −18° C. The internal solution temperature is cooled to −9.0° C. A solution consisting of 2.5 M n-butyllithium in hexane (31 mL, 78 mmol) is added dropwise over 25 minutes (bath temperature −18 to −16° C., internal mixture temperature −9.0 to −0.6° C.), over which time the solution color turned from yellow after addition of the first few drops to orange at the first endpoint. The reaction mixture is stirred for three minutes as the internal mixture temperature cooled to −3.3° C. (bath temperature −14° C.) Another 31 mL of 2.5 M n-butyllithium in hexane is added over 11 minutes (bath temperature −14 to −16° C., internal mixture temperature −3.3 to −0.3° C. with a peak temperature in that time period of +0.2° C.) The reaction mixture is stirred for 31 minutes as the internal mixture temperature cooled to −10.1° C. (bath temperature −14° C.) Cyclopropane-1,1-dicarboxylic acid dimethyl ester (26.0 mL) is added over less than one minute to give an internal mixture temperature of +4.6° C. (bath temperature −13° C.) The reaction mixture is stirred for one hour and is quenched with the addition of brine solution (100 mL.) The layers are separated and the organic phase is dried over anhydrous magnesium sulfate and is concentrated under reduced pressure to afford an oil (59.9 g.) The product is purified by flash silica gel column chromatography to afford the foam product (24.0 g.)

Provenance & Evidence