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

HRID 2093163Notes

Reaction equation

HRID 2093163 reaction equation
[F:1][C:2]([F:21])([F:20])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[NH:15][C@H:14]2[CH3:19])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[H-].[Na+].[Br:24][C:25]1[CH:32]=[CH:31][C:30]([F:33])=[CH:29][C:26]=1[CH2:27]Br>C1COCC1>[F:21][C:2]([F:1])([F:20])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:27][C:26]3[CH:29]=[C:30]([F:33])[CH:31]=[CH:32][C:25]=3[Br:24])[C@H:14]2[CH3:19])[CH:6]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:8]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 5179721-Bromo-2-(bromomethyl)-4-fluorobenzeneHCID 23583229(4S,5R)-5-(3,5-bis(trifluoromethyl)phenyl)-4-methyloxazolidin-2-one

Product 1

HCID 59135189(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-(2-bromo-5-fluorobenzyl)-4-methyl-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (2.0 g, 6.39 mmol) in THF (40 mL) at 0° C. was added NaH (285 mg, 60 w/w % in mineral oil, 7.13 mmol, 1.1 eq.) in one portion. The resulting foaming mixture was stirred in an ice bath. Additional THF (50 mL) was added into the reaction. The mixture was stirred at 0° C. for 30 min. A solution of 2-bromo-5-fluorobenzyl bromide (1.712 g, 6.39 mmol) in THF (20 mL) was added. The resulting mixture was stirred cold for 30 min and then allowed to warm to room temperature. The reaction was completed in 3 hours. The reaction was quenched with NH4Cl (aq., sat.,80 mL). Volatiles were removed in vacuo. The crude mixture was extracted with EtOAc and dried over Na2SO4. The residue was purified by flash chromatography on SiO2 (Biotage 40+M cartridge, EtOAc/hexane, gradient). (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-(2-bromo-5-fluorobenzyl)-4-methyl-1,3-oxazolidin-2-one was obtained as a clear oil. LC-MS: 500.09 (M+1)+. 1H NMR (CDCl3, 500 MHz) δ 7.88 (s, 1H), 7.79 (s, 2H), 7.55 (dd, J=8.8, 5.2 Hz, 1H), 7.17 (dd, J=8.7, 4.5 Hz, 1H), 6.95 (m, 1H), 5.74 (d, J=8.0 Hz, 1H), 4.83 (d, J=15.8, 1H), 4.54 (d, J=16.0 Hz, 1H), 4.11 (m, 1H), 0.80 (d, J=6.6 Hz, 3H).

Workup

  1. stirringThe mixture was stirred at 0° C. for 30 min
  2. stirringThe resulting mixture was stirred cold for 30 min
  3. customThe reaction was quenched with NH4Cl (aq., sat.,80 mL)
  4. customVolatiles were removed in vacuo
  5. extractionThe crude mixture was extracted with EtOAc
  6. dry with materialdried over Na2SO4
  7. customThe residue was purified by flash chromatography on SiO2 (Biotage 40+M cartridge, EtOAc/hexane, gradient)

Sources & evidence

ORD record
ord-6d7166cf86a1420dbfc0cae01daaf877
Source dataset
uspto-grants-2013_05
Patent number
US08440702B2

Reaction notes

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