Methanol → 3-((2-oxo-6-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinolin-1(2H)-yl)methyl)benzoic acid

HRID 1183774Notes

Reaction equation

HRID 1183774 reaction equation
[O:1]=[C:2]1[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:12]3[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=3)[CH:8]=2)[N:3]1[CH2:22][C:23]1[CH:24]=[C:25]([CH:31]=[CH:32][CH:33]=1)[C:26]([O:28]CC)=[O:27].[OH-].[K+].CO>CN(C)C=O>[O:1]=[C:2]1[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:12]3[CH:13]=[CH:14][C:15]([C:18]([F:20])([F:19])[F:21])=[CH:16][CH:17]=3)[CH:8]=2)[N:3]1[CH2:22][C:23]1[CH:24]=[C:25]([CH:31]=[CH:32][CH:33]=1)[C:26]([OH:28])=[O:27]

Participants

5

Reactant 3

HCID 887MethanolHCID 14797Potassium HydroxideHCID 46206945ethyl 3-((2-oxo-6-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinolin-1(2H)-yl)methyl)benzoate

Product 1

HCID 593166123-((2-oxo-6-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinolin-1(2H)-yl)methyl)benzoic acidYield 60%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of ethyl 3-((2-oxo-6-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinolin-1(2H)-yl)methyl)benzoate (45 mg, 0.10 mmol) (PT-094) in N,N-dimethylformamide (2.0 mL) was added 1N potassium hydroxide in methanol (10 mL, 10 mmol). The reaction mixture was stirred at room temperature for 17 hours, and then the solvent was removed under reduced pressure. Water (5.0 mL) was added, and the pH was adjusted to 4-5. The mixture was extracted with ethyl acetate (3×20 mL), and the combined organic phase was washed with 30% ammonium chloride (20 mL), brine (20 mL), dried over magnesium sulfate, and the solvent removed under reduced pressure. The residue was subjected to reverse phase HPLC with a gradient of acetonitrile/water (2% to 98%) to afford 3-((2-oxo-6-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinolin-1(2H)-yl)methyl)benzoic acid (26 mg, 0.06 mmol, 60%) (PT-095). LCMS mz 426.0 M+H), 448.0 (M+Na). 1H NMR (400 MHz; CDCl3) δ 8.06 (bs, 2H); 7.65 (m, 4H); 7.47 (m, 3H); 7.36 (m, 1H); 6.92 (d, J=8.6 Hz, 1H); 5.28 (s, 2H); 3.08 (m, 2H), 2.86 (m, 2H).

Workup

  1. customthe solvent was removed under reduced pressure
  2. additionWater (5.0 mL) was added
  3. extractionThe mixture was extracted with ethyl acetate (3×20 mL)
  4. washthe combined organic phase was washed with 30% ammonium chloride (20 mL), brine (20 mL)
  5. dry with materialdried over magnesium sulfate
  6. customthe solvent removed under reduced pressure

Sources & evidence

ORD record
ord-5dd323e18a9a40b999ac813b0bfa1c65
Source dataset
uspto-grants-2014_03
Patent number
US08664379B2

Reaction notes

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