Dicyclohexylcarbodiimide → 3-(4-(4-(2-Phenyl-1,3-dioxan-5-ylcarbonyl)piperazin-1-yl)-3-fluorophenyl)-5(R)-(isoxazol-3-yloxymethyl)oxazolidin-2-one

Participants

Reaction Steps

To a stirred solution of 2-phenyl-1,3-dioxan-5-ylcarboxylic acid (478 mg, 2.3 mmol) and N-hydroxysuccinimide (291 mg, 2.5 mmol) in anhydrous dichloromethane (25 ml) at 0° was added dicyclohexylcarbodiimide (522 mg, 2.5 mmol). After sitting 1 hour at 0°, N,N-diisopropylethylamine (623 mg, 4.8 mmol) was added, followed by 3-(4-(piperazin-1-yl)-3-fluorophenyl)-5(R)-(isoxazol-3-yloxymethyl)oxazolidin-2-one dihydrochloride (1 g, 2.3 mmol) in portions over 5 minutes. The temperature was allowed to rise to ambient, and stirring continued for 3 hours. Solid was filtered off, washed with dichloromethane (2×20 ml), and the combined organics evaporated to dryness. The residue was purified by chromatography on a 20 g silica Mega Bond Elut® column, eluting with a gradient increasing in polarity from 0 to 10% MeOH in dichloromethane. Relevant fractions were combined and evaporated to give the required product (890 mg) as a mixture of cis and trans isomers.

Provenance & Evidence