Potassium Hydroxide → HCID 57704777, compound

HRID 2093170Notes

Reaction equation

HRID 2093170 reaction equation
[F:1][C:2]([F:50])([F:49])[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:31]=[C:32]([C:37]4[CH:42]=[CH:41][C:40]([C:43]([O:45]C)=[O:44])=[CH:39][C:38]=4[CH3:47])[CH:33]=[CH:34][C:35]=3[Cl:36])[C@H:14]2[CH3:48])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[OH-].[K+]>C(O)C>[F:50][C:2]([F:1])([F:49])[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:31]=[C:32]([C:37]4[CH:42]=[CH:41][C:40]([C:43]([OH:45])=[O:44])=[CH:39][C:38]=4[CH3:47])[CH:33]=[CH:34][C:35]=3[Cl:36])[C@H:14]2[CH3:48])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 25010230HCID 25010230, compound

Product 1

HCID 57704777HCID 57704777, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Methyl 2″-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4′-chloro-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate (25 mg, 0.034 mmol), aqueous potassium hydroxide (300 μL, 3M, 0.90 mmol) and ethanol (2 mL) were stirred at 20° C. overnight. Volatiles were removed under reduced pressure. The resulting residue was treated with brine followed by extraction with ethyl acetate. The combined extracts were dried over Na2SO4 followed by filtration and concentration in vacuo to afford an oil. This oil was purified by preparative TLC on SiO2 (eluted with 50% EtOAc in hexanes) to afford a clear glass. The glass was further purified by reverse phase preparative HPLC (Kromasil 100-5C18, 100×21.1 mm) eluting by a MeCN (0.1% TFA, v/v)/H2O (0.1% TFA, v/v) gradient mixture affording 2″-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4′-chloro-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylic acid. LCMS calc.=715.12; found=716.12 (M+1)+. 1H NMR signals are doubled because of atropisomerism 1H NMR (CDCl3, 500 MHz) δ 7.99 (d, J=8.0 Hz, 1H), 7.92 (d, J=8.5 Hz, 1H), 7.85 (d, J=5 Hz, 1H), 7.72-7.68 (m, 1.5H), 7.67-7.60 (m, 2.5H), 7.47-7.36 (m, 2H), 7.32 (d, J=8.0 Hz, 0.5H), 7.28 (d, J=8.0 Hz, 0.5H), 7.15 (s, 1H), 7.08 (dd, J=8.5, 7.0 Hz, 1H), 5.58 (d, J=8.0 Hz, 0.5H), 5.29 (d, J=6.5 Hz, 0.5H), 4.97 (d, J=15.5 Hz, 0.5H), 4.94 (d, J=14 Hz, 0.5H), 4.16 (d, J=16 Hz, 0.5H), 3.96 (d, J=15.5 Hz, 0.5H), 3.87 (s, 3H), 3.83-3.74 (m, 1H), 2.38, 2.33 (s, 3H), 0.55 (d, J=6.5 Hz, 1.5H), 0.42 (d, J=7 Hz, 1.5H).

Workup

  1. customVolatiles were removed under reduced pressure
  2. additionThe resulting residue was treated with brine
  3. extractionfollowed by extraction with ethyl acetate
  4. dry with materialThe combined extracts were dried over Na2SO4
  5. filtrationfollowed by filtration and concentration in vacuo
  6. customto afford an oil
  7. customThis oil was purified by preparative TLC on SiO2 (eluted with 50% EtOAc in hexanes)
  8. customto afford a clear glass
  9. customThe glass was further purified by reverse phase preparative HPLC (Kromasil 100-5C18, 100×21.1 mm)
  10. washeluting by a MeCN (0.1% TFA, v/v)/H2O (0.1% TFA, v/v) gradient mixture

Sources & evidence

ORD record
ord-b11f6127b443436fbb5a1dbb93564b18
Source dataset
uspto-grants-2013_05
Patent number
US08440702B2

Reaction notes

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