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, 23.97 mmol) in anhydrous ethylene glycol dimethyl ether (DME) (30 mL) is cooled to -20° C., under nitrogen (N2), and freshly distilled diisopropyl-ethylamine (5.0 mL, 28.77 mmol) is added, followed by slow addition of pivaloyl chloride (3.2 mL, 26.37 mmol). The resulting milky slurry is stirred at -20° C. for 30 minutes. The white solid is filtered, washed with DME (5 mL). The lilt rate 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, 1.6M 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 vacuc. 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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