Citric Acid → 2-[2-(3,5-Bis-trifluoromethyl-phenyl)-6-(4-trifluoromethyl-phenyl)-pyridin-4-yl]-4-methyl-pentanoic acid

HRID 2427880Notes

Reaction equation

HRID 2427880 reaction equation
C[O:2][C:3](=[O:39])[CH:4]([C:9]1[CH:14]=[C:13]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=2)[N:12]=[C:11]([C:25]2[CH:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[C:27]([C:35]([F:38])([F:37])[F:36])[CH:26]=2)[CH:10]=1)[CH2:5][CH:6]([CH3:8])[CH3:7].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>[OH-].[Na+].C1COCC1>[F:33][C:31]([F:32])([F:34])[C:29]1[CH:30]=[C:25]([C:11]2[CH:10]=[C:9]([CH:4]([CH2:5][CH:6]([CH3:8])[CH3:7])[C:3]([OH:39])=[O:2])[CH:14]=[C:13]([C:15]3[CH:16]=[CH:17][C:18]([C:21]([F:22])([F:24])[F:23])=[CH:19][CH:20]=3)[N:12]=2)[CH:26]=[C:27]([C:35]([F:36])([F:37])[F:38])[CH:28]=1

Participants

5

Reactant 2

HCID 311Citric AcidHCID 591617352-[2-(3,5-Bis-trifluoromethyl-phenyl)-6-(4-trifluoromethyl-phenyl)-pyridin-4-yl]-4-methyl-pentanoic acid methyl ester

Product 1

HCID 451081112-[2-(3,5-Bis-trifluoromethyl-phenyl)-6-(4-trifluoromethyl-phenyl)-pyridin-4-yl]-4-methyl-pentanoic acidYield 78%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 14798Sodium HydroxideSolvent

Procedure

A solution of 2-[2-(3,5-bis-trifluoromethyl-phenyl)-6-(4-trifluoromethyl-phenyl)-pyridin-4-yl]-4-methyl-pentanoic acid methyl ester (80 mg, 0.14 mmol) in NaOH (1N, 1 mL) and THF (4 mL) was stirred at 40° C. overnight. The mixture was cooled to room temperature, acidified with 10% citric acid, extracted with CH2Cl2 (3×). The organic layer was washed with brine, dried over Na2SO4, filtered and evaporated. The residue was purified by chromatography (5-30% ethyl acetate in CH2Cl2) to give the product as a white solid (60 mg, 78%). 1H NMR (300 MHz, CDCl3) δ 8.55 (s, 2H), 8.23 (d, J=7.91 Hz, 2H), 7.96 (s, 1H), 7.72-7.85 (m, 4H), 3.89 (t, J=7.91 Hz, 1H), 2.08-2.22 (m, 1H), 1.75-1.85 (m, 1H), 1.55-1.68 (m, 1H), 0.99 (d, J=6.40 Hz, 6H). MS m/e 550.2 (M+H).

Workup

  1. extractionextracted with CH2Cl2 (3×)
  2. washThe organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by chromatography (5-30% ethyl acetate in CH2Cl2)

Sources & evidence

ORD record
ord-3643670df0c941ca88cebfa939a8f962
Source dataset
uspto-grants-2011_06
Patent number
US07968725B2

Reaction notes

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