Methanol → HCID 178463696, compound

HRID 505285Notes

Reaction equation

HRID 505285 reaction equation
[F:1][C:2]([F:49])([F:48])[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:42]=[C:41]([C:43]([F:46])([F:45])[F:44])[CH:40]=[CH:39][C:21]=3[CH2:22][N:23]([CH2:26][C@H:27]3[CH2:32][CH2:31][C@H:30]([CH2:33][C:34]([O:36]CC)=[O:35])[CH2:29][CH2:28]3)[CH2:24][CH3:25])[C@H:14]2[CH3:47])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[OH-].[K+].CO>CCO.O>[F:12][C:9]([F:10])([F:11])[C:7]1[CH:6]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:42]=[C:41]([C:43]([F:44])([F:45])[F:46])[CH:40]=[CH:39][C:21]=3[CH2:22][N:23]([CH2:26][C@H:27]3[CH2:28][CH2:29][C@H:30]([CH2:33][C:34]([OH:36])=[O:35])[CH2:31][CH2:32]3)[CH2:24][CH3:25])[C@H:14]2[CH3:47])[CH:4]=[C:3]([C:2]([F:1])([F:49])[F:48])[CH:8]=1

Participants

6

Reactant 3

HCID 887MethanolHCID 14797Potassium HydroxideHCID 178471791HCID 178471791, compound

Product 1

HCID 178463696HCID 178463696, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent2×

Procedure

To a solution of ethyl (trans-4-{[[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4-(trifluoromethyl)benzyl](ethyl)amino]methyl}cyclohexyl)acetate (51 mg, 0.0718 mmol) in EtOH (3 mL) and water (2 mL) was added 4 M KOH (500 μL). The mixture was stirred at room temperature for 30 minutes and then water (1 mL) and MeOH (100 μL) were added. After an additional hour, the reaction was quenched with 1 N HCl (5 mL), diluted with EtOAc (20 mL) and washed with brine (10 mL). The organic layer was dried over Na2SO4, filtered, and concentrated. Purification of the residue by PTLC (50% EtOAc/hexanes with 1% AcOH) was followed by azeotroping of the product with toluene to afford (trans-4-{[[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4-(trifluoromethyl)benzyl](ethyl)amino]methyl}cyclohexyl)acetic acid. Rf=0.13 (50% EtOAc/hexanes with 1% AcOH). LCMS=683.2 (M+1)+. 1H NMR (CDCl3, 500 MHz) δ 7.89 (s, 1H), 7.79 (s, 2H), 7.61-7.53 (m, 2H), 7.48 (s, 1H), 5.74 (d, J=7.8 Hz, 1H), 5.00 (d, J=16.4 Hz, 1H), 4.44 (d, J=16.2 Hz, 1H), 4.04-3.98 (m, 1H), 3.72-3.61 (m, 2H), 2.54-2.53 (m, 2H), 2.23-2.19 (m, 4H), 1.82-1.76 (m, 4H), 1.72-1.64 (m, 1H), 1.39-1.38 (m, 1H), 1.04 (t, J=6.8 Hz, 3H), 0.99-0.78 (m, 4H), 0.76 (d, J=6.8 Hz, 3H).

Workup

  1. waitAfter an additional hour
  2. customthe reaction was quenched with 1 N HCl (5 mL)
  3. additiondiluted with EtOAc (20 mL)
  4. washwashed with brine (10 mL)
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification of the residue by PTLC (50% EtOAc/hexanes with 1% AcOH)
  9. customby azeotroping of the product with toluene

Sources & evidence

ORD record
ord-b574608354764043a19a181357a4131e
Source dataset
uspto-grants-2010_08
Patent number
US07781426B2

Reaction notes

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