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

HRID 1994622Notes

Reaction equation

HRID 1994622 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 8028TetrahydrofuranSolvent2×

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., NaH (285 mg, 60 w/w % in mineral oil, 7.13 mmol, 1.1 eq.) was added 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 TBF (20 mL) was added. The resulting mixture was stirred cold for 30 min and then allowed to warm to ambient. The reaction was completed in 3 h, monitored by LC-MS. The reaction was quenched with saturated aq. NH4Cl (80 mL). Volatiles were removed in vacuo. Crude mixture was extracted with EtOAc, and dried over Na2SO4. The resulting clear gel was purified by SiO2 (Biotage 40+M cartridge, EtOAc/hexane, gradient). The titled compound 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. temperatureto warm to ambient
  4. customThe reaction was quenched with saturated aq. NH4Cl (80 mL)
  5. customVolatiles were removed in vacuo
  6. extractionCrude mixture was extracted with EtOAc
  7. dry with materialdried over Na2SO4
  8. customThe resulting clear gel was purified by SiO2 (Biotage 40+M cartridge, EtOAc/hexane, gradient)

Sources & evidence

ORD record
ord-e87c875a69c145bd9b7b4a79202588f7
Source dataset
uspto-grants-2010_01
Patent number
US07652049B2

Reaction notes

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