Triphenylmethane → (4R-cis)-3-[(10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5-yl)acetyl]-4-methyl-5-phenyl-2-oxazolidinone

Temperature

-20 °C

A solution of 10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5-acetic acid (12.0 g, 47.56 mmol) in anhydrous ethylene glycol dimethyl ether (DME) (60 mL) is cooled to -20° C. under nitrogen, and freshly distilled diisopropylethyl amine (9.9 mL, 57.07 mmol) is added, followed by slow addition of pivaloyl chloride (6.4 mL, 52.32 mmol). The resulting milky slurry is stirred at -20° C. for 30 minutes. The white solid is filtered, washed with DME (10 mL). The filtrate of the mixed anhydride is cooled to -78° C. under a nitrogen atmosphere. In a separate flask, (4R)-methyl-(5S)-phenyl-2-oxazolidinone (9.3 g, 52.32 mmol) (Example A) is dissolved in freshly distilled tetrahydrofuran (100 mL) and cooled to -78° C. under argon. Several crystals of triphenylmethane is added as an indicator. To this solution is added n-butyllithium (34.3 mL, 54.93 mmol, 1.6 M solution in hexane). The red solution is stirred at -78° C. for 5 minutes, and the solution of the 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. The tetrahydrofuran is removed in vacuo and the residue is extracted with dichloromethane (3×200 mL). The organic extracts are combined and washed successively with aqueous sodium bicarbonate solution, brine, dried (magnesium sulfate), and concentrated in vacuo. The resulting yellow solid is recrystallized from hexane-ethyl acetate/4:1 to give the title compound as a white solid, 16.2 g; mp 133°-134° C.; [α]D =+14.0° (c=1.0, chloroform).

1. filtrationThe white solid is filtered
2. washwashed with DME (10 mL)
3. temperatureThe filtrate of the mixed anhydride is cooled to -78° C. under a nitrogen atmosphere
4. temperaturecooled to -78° C. under argon
5. stirringThe red solution is stirred at -78° C. for 5 minutes
6. additionis added via cannula
7. stirringThe resulting light yellow solution is stirred at -78° C. for 15 minutes
8. temperaturewarmed to room temperature over 2 hours
9. customThe reaction is quenched by addition of aqueous ammonium chloride
10. customThe tetrahydrofuran is removed in vacuo
11. extractionthe residue is extracted with dichloromethane (3×200 mL)
12. washwashed successively with aqueous sodium bicarbonate solution, brine
13. dry with materialdried (magnesium sulfate)
14. concentrationconcentrated in vacuo
15. customThe resulting yellow solid is recrystallized from hexane-ethyl acetate/4:1

ORD record

ord-fed26e51d50f4badb9e2b4165eec50b7

Source dataset

uspto-grants-1993_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05264577