Sodium hydride → 5-[3,5-Bis(trifluoromethyl)phenyl]-3-[2-iodo-5-(trifluoromethyl)benzyl]1,3-oxazolidin-2-one

HRID 1028526

Reaction equation

HRID 1028526 reaction equation
[H-].[Na+].[F:3][C:4]([F:22])([F:21])[C:5]1[CH:6]=[C:7]([CH:15]2[O:19][C:18](=[O:20])[NH:17][CH2:16]2)[CH:8]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:10]=1.Br[CH2:24][C:25]1[CH:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[CH:27][C:26]=1[I:35]>C1COCC1>[F:22][C:4]([F:3])([F:21])[C:5]1[CH:6]=[C:7]([CH:15]2[O:19][C:18](=[O:20])[N:17]([CH2:24][C:25]3[CH:30]=[C:29]([C:31]([F:32])([F:34])[F:33])[CH:28]=[CH:27][C:26]=3[I:35])[CH2:16]2)[CH:8]=[C:9]([C:11]([F:12])([F:13])[F:14])[CH:10]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 184515342-(Bromomethyl)-1-iodo-4-(trifluoromethyl)benzeneHCID 591350695-[3,5-Bis(trifluoromethyl)phenyl]-1,3-oxazolidin-2-one

Product 1

HCID 591352395-[3,5-Bis(trifluoromethyl)phenyl]-3-[2-iodo-5-(trifluoromethyl)benzyl]1,3-oxazolidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A stirred suspension of sodium hydride (60% in oil, 167 mg, 4.18 mmol) in THF (5 mL) was treated at 0° C. with 5-[3,5-bis(trifluoromethyl)phenyl]-1,3-oxazolidin-2-one (500 mg, 1.67 mmol) dissolved in THF (1 mL), under an atmosphere of N2. The reaction was stirred for 20 min and a solution of 2-(bromomethyl)-1-iodo-4-(trifluoromethyl)benzene (610 mg, 1.67 mmol) in THF (1 mL) was added dropwise. The reaction was stirred at room temperature for 18 h. The reaction was quenched with H2O (1 mL) and partitioned between EtOAc (80 mL) and H2O (25 mL). The aqueous phase was re-extracted with EtOAc (2×20 mL) and the combined organic extracts were washed with brine (30 mL), dried (MgSO4) and concentrated in vacuo to give the crude product. This was purified by flash silica-gel chromatography (0-30% EtOAc in hexanes gradient) to afford 5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-iodo-5-(trifluoromethyl)benzyl]1,3-oxazolidin-2-one. Rf=0.55 (515% EtOAc/hexanes). LCMS 584 (M+1)+. 1H NMR (CDCl3, 500 MHz) δ 8.05 (d, J=8.2 Hz, 1H), 7.95 (br s, 1H), 7.85 (br s, 2H), 7.51 (br s, 1H), 7.32 (m, 1H), 5.72 (t, J=8.0 Hz, 1 H), 4.74 (d, J=15.5 Hz, 1H), 4.64 (d, J=15.3 Hz), 4.14 (t, J=7.1 Hz, 1H), 3.47 (dd, J=7.1, 1.6 Hz).

Workup

  1. stirringThe reaction was stirred at room temperature for 18 h
  2. customThe reaction was quenched with H2O (1 mL)
  3. custompartitioned between EtOAc (80 mL) and H2O (25 mL)
  4. extractionThe aqueous phase was re-extracted with EtOAc (2×20 mL)
  5. washthe combined organic extracts were washed with brine (30 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customto give the crude product
  9. customThis was purified by flash silica-gel chromatography (0-30% EtOAc in hexanes gradient)

Sources & evidence

ORD record
ord-46f7b56c3a784e96b40be9d2e0573394
Source dataset
uspto-grants-2014_05
Patent number
US08735435B2

Linked notes

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