Ammonium Chloride → (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-[2-nitro-5-(trifluoromethoxy)benzyl]-1,3-oxazolidin-2-one

HRID 1028596Notes

Reaction equation

HRID 1028596 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.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].Br[CH2:33][C:34]1[CH:39]=[C:38]([O:40][C:41]([F:44])([F:43])[F:42])[CH:37]=[CH:36][C:35]=1[N+:45]([O-:47])=[O:46].[NH4+].[Cl-]>CC(N(C)C)=O.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]([CH2:33][C:34]3[CH:39]=[C:38]([O:40][C:41]([F:44])([F:43])[F:42])[CH:37]=[CH:36][C:35]=3[N+:45]([O-:47])=[O:46])[C@H:14]2[CH3:19])[CH:6]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:8]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 23583229(4S,5R)-5-(3,5-bis(trifluoromethyl)phenyl)-4-methyloxazolidin-2-oneHCID 667165912-Nitro-5-(trifluoromethoxy)benzyl bromide

Product 1

HCID 86603424(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-[2-nitro-5-(trifluoromethoxy)benzyl]-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent2×

Procedure

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (840 mg, 2.68 mmol) in DMA (25 mL) was added NaHMDS (2.68 mL of a 1M solution in THF, 2.68 mmol). The reaction was stirred at room temperature for 5 minutes, and then 2-(bromomethyl)-1-nitro-4-(trifluoromethoxy)benzene (967 mg, 3.22 mmol) was added by cannula in DMA (5 mL). After 15 minutes, the reaction was poured into saturated NH4Cl (50 mL). The mixture was extracted with EtOAc (150 mL) and the organic layer was washed with water and brine (40 mL each). The organic layer was dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography on silica gel (5 to 25% EtOAc/hexanes) afforded (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-[2-nitro-5-(trifluoromethoxy)benzyl]-1,3-oxazolidin-2-one. Rf=0.10 (15% EtOAc/hexanes). LCMS=533.2 (M+1)+. 1H NMR (CDCl3, 500 MHz) δ 8.16 (d, J=8.9 Hz, 1H), 7.92 (s, 1H), 7.80 (s, 2H), 7.44 (s, 1H), 7.33 (d, J=8.9 Hz, 1H), 5.78 (d, J=7.8 Hz, 1H), 4.94 (d, J=17.0 Hz, 1H), 4.79 (d, J=16.9 Hz, 1H), 4.25 (m, 1H), 0.81 (d, J=6.7 Hz, 3H).

Workup

  1. waitAfter 15 minutes
  2. extractionThe mixture was extracted with EtOAc (150 mL)
  3. washthe organic layer was washed with water and brine (40 mL each)
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification of the residue by flash chromatography on silica gel (5 to 25% EtOAc/hexanes)

Sources & evidence

ORD record
ord-55f6858654734de0adce1d81c8f68db5
Source dataset
uspto-grants-2014_05
Patent number
US08735435B2

Reaction notes

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