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

HRID 1028534Notes

Reaction equation

HRID 1028534 reaction equation
[H-].[Na+].[F:3][C:4]([F:23])([F:22])[C:5]1[CH:6]=[C:7]([C@H:15]2[O:19][C:18](=[O:20])[NH:17][C@H:16]2[CH3:21])[CH:8]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:10]=1.Br[CH2:25][C:26]1[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[CH:28][C:27]=1[I:36]>C1COCC1>[F:23][C:4]([F:3])([F:22])[C:5]1[CH:6]=[C:7]([C@H:15]2[O:19][C:18](=[O:20])[N:17]([CH2:25][C:26]3[CH:31]=[C:30]([C:32]([F:33])([F:35])[F:34])[CH:29]=[CH:28][C:27]=3[I:36])[C@H:16]2[CH3:21])[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 23583229(4S,5R)-5-(3,5-bis(trifluoromethyl)phenyl)-4-methyloxazolidin-2-one

Product 1

HCID 53363742(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-iodo-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-oneYield 82.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

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).

Workup

  1. customThe reaction was carefully quenched with H2O (15 mL)
  2. custompartitioned between EtOAc (250 mL) and H2O (75 mL)
  3. extractionThe aqueous layer was extracted with EtOAc (3×100 mL)
  4. washCombined organic layers were washed with brine (100 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography (0-20% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-8e87e6900e5348e885b1686abc8205f6
Source dataset
uspto-grants-2014_05
Patent number
US08735435B2

Reaction notes

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