Water → HCID 11642706, compound

HRID 1994547Notes

Reaction equation

HRID 1994547 reaction equation
[F:1][C:2]([F:37])([F:36])[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:34]=[CH:33][NH:32][CH:31]=3)[C@H:14]2[CH3:35])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[OH-].[K+].I[CH:41]([CH3:43])[CH3:42].O>CS(C)=O>[F:37][C:2]([F:1])([F:36])[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:34]=[CH:33][N:32]([CH:41]([CH3:43])[CH3:42])[CH:31]=3)[C@H:14]2[CH3:35])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6362Isopropyl iodideHCID 14797Potassium HydroxideHCID 11555615HCID 11555615, compound

Product 1

HCID 11642706HCID 11642706, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-[2-(1H-pyrrol-3-yl)-5-(trifluoromethyl)benzyl]-1,3-oxazolidin-2-one (6.8 mg, 0.0127 mmol) (Example 120) in DMSO (300 μL) was added powdered KOH (3.6 mg, 0.0643 mmol). After stirring for 15 minutes, 2-iodopropane (3.2 μL, 0.032 mmol) was added. After 1.5 hours of stirring at room temperature, water (5 mL) was added, and the mixture was extracted, first with CH2Cl2 (2×15 mL) and then with EtOAc (2×15 mL). The combined organics were dried over Na2SO4, filtered, and concentrated. Purification of the residue by PTLC (25% EtOAc/hexanes) afforded (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-(1-isopropyl-1H-pyrrol-3-yl)-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one. Rf=0.33 (25% EtOAc/hexanes). LCMS=579.2 (M+i)+. 1H NMR (CDCl3, 500 MHz) δ 7.85 (s, 1H), 7.71 (s, 2H), 7.61 (s, 1H), 7.56 (d, J=8.0 Hz, 1H), 7.50 (d, J=8.0 Hz, 1H), 6.83 (t, J=2.1 Hz, 1H), 6.79 (t, J=2.5 Hz, 1H), 6.24 (t, J=2.3 Hz, 1H), 5.49 (d, J=8.0 Hz, 1H), 5.04 (d, J=15.5 Hz, 1H), 4.48 (d, J=15.6 Hz, 1H), 4.27 (m, 1H), 3.76 (m, 1H), 1.48 (d, J=6.6 Hz, 6H), 0.49 (d, J=6.6 Hz, 3H).

Workup

  1. stirringAfter 1.5 hours of stirring at room temperature
  2. extractionthe mixture was extracted, first with CH2Cl2 (2×15 mL)
  3. dry with materialThe combined organics were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification of the residue by PTLC (25% EtOAc/hexanes)

Sources & evidence

ORD record
ord-f099f40e790d48c98a7012dd9dc0400b
Source dataset
uspto-grants-2010_01
Patent number
US07652049B2

Reaction notes

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