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

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (5.3 g, 16.95 mmol) in THF (100 mL) at 0° C., NaH (746 mg, 60 w/w % in mineral oil, 18.65 mmol, 1.1 eq.) was added in one portion. The resulting foaming mixture was stirred in an ice bath. Additional THF (100 mL) was added into the reaction. The mixture was stirred at 0° C. for 30 min. A solution of 1-bromo-2-(bromomethyl)-4-nitrobenzene (5.0 g, 16.95 mmol) in THF (25 mL) was added. The resulting mixture was stirred cold for 30 min and then allowed to warm to ambient. The reaction was completed in 1.5 h. The reaction was quenched with sat. aqueous NH4Cl (100 mL). Crude mixture was extracted with EtOAc, and dried over Na2SO4. The resulting clear gel was purified by SiO2 (Biotage 40M cartridge, EtOAc/hexane, gradient, 25% to 45%). The titled compound was obtained as a crystalline solid. LC-MS: 529.11 (M+1)+. 1H NMR (CDCl3, 500 MHz) δ 8.24 (d, J=2.5 Hz, 1H), 8.07 (dd, J=8.7, 2.8 Hz, 1H), 7.91 (s, 1H), 7.79-7.83 (m, 3H), 5.82 (d, J=7.8 Hz, 1H), 4.82 (d, J=16.2 Hz, 1H), 4.44 (d, J=16.3, 1H), 4.11-4.20 (m, 1H), 0.84 (d, J=6.6 Hz, 3H).

1. stirringThe mixture was stirred at 0° C. for 30 min
2. stirringThe resulting mixture was stirred cold for 30 min
3. temperatureto warm to ambient
4. customThe reaction was quenched with sat. aqueous NH4Cl (100 mL)
5. extractionCrude mixture was extracted with EtOAc
6. dry with materialdried over Na2SO4
7. customThe resulting clear gel was purified by SiO2 (Biotage 40M cartridge, EtOAc/hexane, gradient, 25% to 45%)

ORD record

ord-fa12188bf3ee4cc1aa04c3d971ca255c

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08735435B2