Citric Acid → HCID 178464360, compound

HRID 505309Notes

Reaction equation

HRID 505309 reaction equation
[F:1][C:2]([F:48])([F:47])[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[N:30]([CH2:33][C@H:34]3[CH2:39][CH2:38][C@H:37]([CH2:40][C:41]([O:43]CC)=[O:42])[CH2:36][CH2:35]3)[CH2:31][CH3:32])[C@H:14]2[CH3:46])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[OH-].[K+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CCO>[F:48][C:2]([F:1])([F:47])[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[N:30]([CH2:33][C@H:34]3[CH2:35][CH2:36][C@H:37]([CH2:40][C:41]([OH:43])=[O:42])[CH2:38][CH2:39]3)[CH2:31][CH3:32])[C@H:14]2[CH3:46])[CH:6]=[C:7]([C:9]([F:10])([F:12])[F:11])[CH:8]=1

Participants

5

Reactant 3

HCID 311Citric AcidHCID 14797Potassium HydroxideHCID 178471775HCID 178471775, compound

Product 1

HCID 178464360HCID 178464360, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a stirred 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)phenyl](ethyl)amino]methyl}cyclohexyl)acetate (Step C; 29 mg; 0.042 mmol) in EtOH (2 mL) was added 4 M KOH (400 μL). The reaction was stirred for 90 min, neutralized with aq. citric acid and partitioned between EtOAc (10 mL) and H2O (10 mL). The aqueous layer was re-extracted with EtOAc (10 mL) and the combined organic layers were washed with brine (10 mL), dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by preparatory silica gel chromatography (eluted with 2:1 Hexanes:EtOAc+1% AcOH) 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)phenyl](ethyl)amino]methyl}cyclohexyl)acetic acid as a clear glass. LCMS=669.2 (M+1)+. 1H NMR (CDCl3, 500 MHz): δ 7.91 (s, 1 H), 7.80 (s, 2 H), 7.57 (s, 1 H), 7.52 (d, J=8.3 Hz, 1H), 7.22 (d, J=8.5 Hz, 1 H), 5.77 (d, J=8.0 Hz, 1 H), 4.79 (d, J=16.2 Hz, 1 H), 4.57 (d, J=16.2 Hz, 1H), 4.02-3.99 (m, 1 H), 3.05-2.95 (m, 2 H), 2.93-2.84 (m, 2 H), 2-19 (d, J=6.9 Hz, 2 H), 1.82-1.75 (m, 4H), 1.74-1.68 (m, 1 H), 1.43-1.37 (m, 1 H), 1.01 (t, J=7.0 Hz, 3 H), 0.99-0.88 (m, 4 H), 0.66 (d, J=6.4 Hz, 3 H).

Workup

  1. custompartitioned between EtOAc (10 mL) and H2O (10 mL)
  2. extractionThe aqueous layer was re-extracted with EtOAc (10 mL)
  3. washthe combined organic layers were washed with brine (10 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by preparatory silica gel chromatography (eluted with 2:1 Hexanes:EtOAc+1% AcOH)

Sources & evidence

ORD record
ord-7bcd5f6a76264c9c8e8fb0ffcee42e77
Source dataset
uspto-grants-2010_08
Patent number
US07781426B2

Reaction notes

Loading…