Potassium Carbonate → 4-{4-[3-Benzoyl-8-(trifluoromethyl)quinolin-4-yl]phenoxymethyl}benzoic acid

HRID 2104503Notes

Reaction equation

HRID 2104503 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[C:12](=[C:13]([C:18]([F:21])([F:20])[F:19])[CH:14]=[CH:15][CH:16]=3)[N:11]=[CH:10][C:9]=2[C:22]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:23])=[CH:4][CH:3]=1.Br[CH2:31][C:32]1[CH:41]=[CH:40][C:35]([C:36]([O:38]C)=[O:37])=[CH:34][CH:33]=1.C([O-])([O-])=O.[K+].[K+]>CC(C)=O>[C:22]([C:9]1[CH:10]=[N:11][C:12]2[C:17]([C:8]=1[C:5]1[CH:4]=[CH:3][C:2]([O:1][CH2:31][C:32]3[CH:41]=[CH:40][C:35]([C:36]([OH:38])=[O:37])=[CH:34][CH:33]=3)=[CH:7][CH:6]=1)=[CH:16][CH:15]=[CH:14][C:13]=2[C:18]([F:21])([F:19])[F:20])(=[O:23])[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 256687Methyl 4-(bromomethyl)benzoateHCID 135518299[4-(4-Hydroxyphenyl)-8-(trifluoromethyl)quinolin-3-yl](phenyl)methanone

Product 1

HCID 160903284-{4-[3-Benzoyl-8-(trifluoromethyl)quinolin-4-yl]phenoxymethyl}benzoic acidYield 47%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A solution of [4-(4-hydroxyphenyl)-8-(trifluoromethyl)quinolin-3-yl](phenyl) methanone (0.5 g, 1.3 mmol), methyl 4-bromomethylbenzoate(0.30 g, 1.3 mmol) and K2CO3 (0.42 g, 3 mmol) in acetone (20 ml) was heated to reflux. After 1 hr, the reaction was cooled, filtered and concentrated. The resulting oil was dissolved in THF/MeOH (20 ml) and treated with 2N NaOH (2 ml) and heated to reflux. After 1 hr, the reaction was cooled, poured into 2N HCl and extracted with EtOAc. The organic layer was dried, concentrated to give a solid which was triturated with 10% EtOAc/hexane, filtered to give the desired compound (0.32 g, Yield=47%); MS (ESI) m/z 528 ([M+H]+); 1H NMR (DMSO) δ 12.98 (bs, 1H), 9.11 (s, 1H), 8.33 (d, 1H, J=6.8 Hz), 7.96-7.91 (m, 3H), 7.82-7.77 (m, 1H), 7.64-7.53 (m, 5H), 7.39-7.35 (m, 2H), 7.27 (d, 2H, J=7.8 Hz), 6.99 (d, 2H, J=7.8 Hz), 5.17 (s, 2H).

Workup

  1. temperaturethe reaction was cooled
  2. filtrationfiltered
  3. concentrationconcentrated
  4. dissolutionThe resulting oil was dissolved in THF/MeOH (20 ml)
  5. additiontreated with 2N NaOH (2 ml)
  6. temperatureheated to reflux
  7. waitAfter 1 hr
  8. temperaturethe reaction was cooled
  9. additionpoured into 2N HCl
  10. extractionextracted with EtOAc
  11. customThe organic layer was dried
  12. concentrationconcentrated
  13. customto give a solid which
  14. customwas triturated with 10% EtOAc/hexane
  15. filtrationfiltered

Sources & evidence

ORD record
ord-c0aa158daeaa4e10bb2512ac2323730c
Source dataset
uspto-grants-2009_08
Patent number
US07576215B2

Reaction notes

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