Potassium Hydroxide → HCID 178461487, compound

HRID 505314Notes

Reaction equation

HRID 505314 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:25]=[C:24]([O:26][C:27]([F:30])([F:29])[F:28])[CH:23]=[CH:22][C:21]=3[N:31]([CH3:46])[C:32]([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)=[O:33])[C@H:14]2[CH3:47])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[OH-].[K+]>CCO>[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:25]=[C:24]([O:26][C:27]([F:30])([F:28])[F:29])[CH:23]=[CH:22][C:21]=3[N:31]([CH3:46])[C:32]([C@H:34]3[CH2:39][CH2:38][C@H:37]([CH2:40][C:41]([OH:43])=[O:42])[CH2:36][CH2:35]3)=[O:33])[C@H:14]2[CH3:47])[CH:4]=[C:3]([C:2]([F:1])([F:49])[F:48])[CH:8]=1

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 178471798HCID 178471798, compound

Product 1

HCID 178461487HCID 178461487, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

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-(trifluoromethoxy)phenyl](methyl)amino]carbonyl}cyclohexyl)acetate (100 mg; 0.14 mmol) in EtOH (110 mL) was treated dropwise with 4 M KOH (1 mL). The reaction was stirred at room temperature and quenched with 10% citric acid after 2.5 h. The reaction was partitioned between EtOAc (50 mL) and H2O (50 mL) and the aqueous layer was extracted with EtOAc (3×50 mL). The combined extracts were washed with brine (50 mL), dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by reverse-phase HPLC and the desired product was lyophilized to afford (trans-4-{[[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4-(trifluoromethoxy)phenyl](methyl)amino]carbonyl}cyclohexyl)acetic acid as a white solid. LCMS=685.0 (M+1)+. 1H NMR (CDCl3, 500 MHz, mixture of atropisomers): δ 7.92 (s, 1 H), 7.80 (s, 1 H), 7.74 (s, 1 H), 7.29-7.21 (m, 2 H), 7.17-7.15 (m, 1 H), 5.67 (d, J=8.2 Hz, 1 H), 4.96 (d, J=14.7 Hz, 1 H), 4.22 (d, J=16.5 Hz, 1 H), 3.88 (d, J=15.1 Hz, 1 H), 3.41 (s, 3 H), 2.73-2.66 (m, 1 H), 2.28-2.24 (m, 1 H), 2.15-2.12 (m, 1 H), 2.01-1.50 (m, 8 H), 1.18-1.10 (m, 1 H), 0.76-0.68 (m, 3 H).

Workup

  1. customquenched with 10% citric acid after 2.5 h
  2. customThe reaction was partitioned between EtOAc (50 mL) and H2O (50 mL)
  3. extractionthe aqueous layer was extracted with EtOAc (3×50 mL)
  4. washThe combined extracts were washed with brine (50 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by reverse-phase HPLC

Sources & evidence

ORD record
ord-b83547f23b3b44f58b0a740df37b47f5
Source dataset
uspto-grants-2010_08
Patent number
US07781426B2

Reaction notes

Loading…