Sodium Hydroxide → HCID 11592565, compound

HRID 1028644Notes

Reaction equation

HRID 1028644 reaction equation
[F:1][C:2]([F:44])([F:43])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][C:21]=3[C:30]3[CH:35]=[C:34]([C:36]([CH3:38])=[CH2:37])[C:33]([F:39])=[CH:32][C:31]=3[O:40]C)[C@H:14]2[CH3:42])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[Cl-].[Li+].[OH-].[Na+]>CN(C=O)C>[F:44][C:2]([F:1])([F:43])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([C:26]([F:28])([F:29])[F:27])[CH:23]=[CH:22][C:21]=3[C:30]3[CH:35]=[C:34]([C:36]([CH3:38])=[CH2:37])[C:33]([F:39])=[CH:32][C:31]=3[OH:40])[C@H:14]2[CH3:42])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 433294Lithium ChlorideHCID 11635929HCID 11635929, compound

Product 1

HCID 11592565HCID 11592565, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
160 °C

Procedure

To a stirred solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[4′-fluoro-5′-isopropenyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one (Example 300, 50 mg, 0.078 mmol) in DMF (450 μL) was added lithium chloride (13.4 mg, 0.315 mmol). The vial was sealed and the reaction was heated at 160° C. for 14 h. 10% NaOH (10 mL) was added and the resultant solution was extracted with ether (3×10 mL). The aqueous layer was acidified to pH˜3 with 3N HCl and was re-extracted with ether (3×25 mL). The combined organic extracts were washed with brine (25 mL), dried (MgSO4), filtered, and concentrated in vacuo. The crude product was purified by flash silica gel chromatography (0-25% EtOAc/hexanes gradient) to afford (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[4′-fluoro-2′-hydroxy-5′-isopropenyl-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one as a clear glass. LCMS=622.1 (M+1)+. 1H NMR (CDCl3, 500 MHz, mixture of atropisomers): δ 7.90 (s, 1 H), 7.76-7.70 (m, 4 H), 7.48-7.45 (m, 1 H), 7.11-7.07 (m, 1 H), 6.75 (d, J=11.7 Hz, 1 H), 5.71 (d, J=7.8 Hz, 1 H), 5.59-5.56 (m, 1 H), 5.25-5.21 (m, 2 H), 4.81 (d, J=15.4 Hz, 1 H), 4.04 (d, J=15.6 Hz, 1 H), 3.97-3.92 (m, 1 H), 2.13 (s, 3 H), 0.58 (d, J=6.6 Hz, 3 H).

Workup

  1. customThe vial was sealed
  2. extractionthe resultant solution was extracted with ether (3×10 mL)
  3. extractionwas re-extracted with ether (3×25 mL)
  4. washThe combined organic extracts were washed with brine (25 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by flash silica gel chromatography (0-25% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-59dd3cb9e3df490b8aa04fed077b9af5
Source dataset
uspto-grants-2014_05
Patent number
US08735435B2

Reaction notes

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