1,2-Dimethoxyethane → (4R-cis)-3-[(5H-Dibenzo[a,d]cyclohepten-5-yl)acetyl]-4-methyl-5 phenyl-2-oxazolidinone

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Reaction Conditions

Reaction Steps

A solution of acid from Step A (6.0 g, 3.97 mmol) in anhydrous ethylene glycol dimethyl ether (DME) (30 mL) is cooled to -20° C., under nitrogen (N2), and freshly distilled diisopropylethylamine (5.0 mL, 28.77 mmol) is added, followed by slow addition of pivaloyl chloride (3.2 mL, 6.37 mmol). The resulting milky slurry is stirred at -20° C. for 30 minutes. The white solid is filtered, washed with DME (5 mL). The filtrate of the mixed anhydride is cooled to -78° C. under nitrogen atmosphere. In a separate flask, (4R)-methyl-(5S)-phenyl-2-oxazolidinone (4.7 g, 26.37 mmol) is dissolved in freshly distilled tetrahydrofuran (THF) (53 mL) and cooled to -78° C., under argon (Ar). Several crystals of triphenylmethane (Ph3CH) is added as an indictor. To this solution is added n-butyllithium (n BuLi) (17.3 mL, 27.81 mmol, 1.6 M solution in hexane). The red solution is stirred at -78° C. for 5 minutes, and the solution of mixed anhydride prepared as described above, is added via cannula. The resulting light yellow solution is stirred at -78° C. for 15 minutes and then warmed to room temperature over 2 hours. The reaction is quenched by addition of aqueous ammonium chloride (NH4Cl). The THF is removed in vacuo and the residue is extracted with dichloromethane (CH2Cl2) (3×100 mL). The organic extracts are combined and washed successively with aqueous sodium bicarbonate solution brine (NaHCO3), dried over MgSO4, and concentrated in vacuo. The resulting yellow solid is recrystallized from hexane-AcOEt/2:1 to give the title compound as a white solid, 6.3 g; mp 172°-173° C., [α]D =+10.1° (c=1.0, CHCl3).

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