Sodium hydride → (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-iodo-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one

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Reaction Steps

To a stirred suspension of sodium hydride (60% dispersion in mineral oil; 1.3 g; 0.0325 mol) in THF (60 mL) at 0° C. under N2 was added dropwise a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (Example 17) (4.077 g; 0.013 mol) in THF (50 mL). Gas evolution was observed. The resultant mixture stirred at 0° C. for 30 min prior to addition of a solution of 2-(bromomethyl)-1-iodo-4-(trifluoromethyl)benzene (4.754 g; 0.013 mol) in THF (20 mL). The reaction was allowed to warm to room temperature and stirred for 14 h. The reaction was carefully quenched with H2O (15 mL) and partitioned between EtOAc (250 mL) and H2O (75 mL). The aqueous layer was extracted with EtOAc (3×100 mL). Combined organic layers were washed with brine (100 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by flash chromatography (0-20% EtOAc/hexanes gradient) to afford 6.4 g (82.5%) of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-iodo-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one as a white solid. LCMS=598.1 (M+1)+. 1H NMR (CDCl3, 500 MHz): δ 8.03 (d, J=8.2 Hz, 1 H), 7.90 (s, 1 H), 7.79 (s, 2 H), 7.58 (s, 1 H), 7.30 (dd, J=8.2 Hz, J=2.0 Hz, 1 H), 5.76 (d, J=8 Hz, 1 H), 4.88 (d, J=15.8 Hz, 1 H), 4.37 (d, J=15.8 Hz, 1 H), 4.09-4.02 (m, 1 H), 0.8 (d, J=6.6 Hz, 3 H).

Provenance & Evidence