Sodium bis(trimethylsilyl)amide → (4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one

HRID 1994507Notes

Reaction equation

HRID 1994507 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+].[CH3:32][O:33][C:34]1[C:35]([C:43]2[CH:48]=[CH:47][C:46]([C:49]([F:52])([F:51])[F:50])=[CH:45][C:44]=2[CH2:53]Br)=[CH:36][C:37]([CH:40]([CH3:42])[CH3:41])=[CH:38][CH:39]=1>C1COCC1.CC(N(C)C)=O>[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]([CH2:53][C:44]3[CH:45]=[C:46]([C:49]([F:50])([F:51])[F:52])[CH:47]=[CH:48][C:43]=3[C:35]3[CH:36]=[C:37]([CH:40]([CH3:42])[CH3:41])[CH:38]=[CH:39][C:34]=3[O:33][CH3:32])[C@H:14]2[CH3:19])[CH:6]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:8]=1

Participants

6

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 533636432-(Bromomethyl)-5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenylHCID 86603412(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one

Product 1

HCID 53363913(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent2×

Procedure

((4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]4-methyl-1,3-oxazolidin-2-one) (46.2 mg, 0.148 mmol) was placed in a dry flask and DMA (3 mL) was added. NaHMDS (296 μL of a 1M solution in THF, 0.296 mmol) was added and the reaction was stirred for 5 min. At this time, 2′-(bromomethyl)-5-isopropyl-4′-(trifluoromethyl)biphenyl-2-yl methyl ether (80.0 mg, 0.207 mmol) was added by cannula in DMA (2 mL). After 30 min, the reaction was quenched with saturated NH4Cl (2 mL). The mixture was diluted with EtOAc (40 mL). The organic layer was washed with water (15 mL), and brine (15 mL), dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography with 25% EtOAc/hexanes afforded (4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}4-methyl-1,3-oxazolidin-2-one. Rf=0.27 (25% EtOAc/hexanes). LCMS=620.2 (M+1)+. 1H NMR (CDCl3, 500 MHz; atropisomers present) δ 6.90-7.88 (m, 9H), 4.04-5.05 (m, 3H), 3.25-3.74 (m, 4H), 2.88 (m, 1H), 1.19-1.24 (m, 6H), 0.99-1.07 (m, 3H).

Workup

  1. waitAfter 30 min
  2. customthe reaction was quenched with saturated NH4Cl (2 mL)
  3. additionThe mixture was diluted with EtOAc (40 mL)
  4. washThe organic layer was washed with water (15 mL), and brine (15 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification of the residue by flash chromatography with 25% EtOAc/hexanes

Sources & evidence

ORD record
ord-58837529822748ddb5d5efd676263983
Source dataset
uspto-grants-2010_01
Patent number
US07652049B2

Reaction notes

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