Citric Acid → 2-[2-(4-Fluoro-phenyl)-6-(4-trifluoromethyl-phenyl)-pyridin-4-yl]-4-methyl-pentanoic acid

HRID 2427875Notes

Reaction equation

HRID 2427875 reaction equation
C[O:2][C:3](=[O:32])[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]=[CH:29][C:28]([F:31])=[CH:27][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:31][C:28]1[CH:27]=[CH:26][C:25]([C:11]2[CH:10]=[C:9]([CH:4]([CH2:5][CH:6]([CH3:8])[CH3:7])[C:3]([OH:32])=[O:2])[CH:14]=[C:13]([C:15]3[CH:16]=[CH:17][C:18]([C:21]([F:24])([F:22])[F:23])=[CH:19][CH:20]=3)[N:12]=2)=[CH:30][CH:29]=1

Participants

5

Reactant 2

HCID 311Citric AcidHCID 591617082-[2-(4-Fluoro-phenyl)-6-(4-trifluoromethyl-phenyl)-pyridin-4-yl]-4-methyl-pentanoic acid methyl ester

Product 1

HCID 451080762-[2-(4-Fluoro-phenyl)-6-(4-trifluoromethyl-phenyl)-pyridin-4-yl]-4-methyl-pentanoic acidYield 77.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 14798Sodium HydroxideSolvent

Procedure

A solution of 2-[2-(4-fluoro-phenyl)-6-(4-trifluoromethyl-phenyl)-pyridin-4-yl]-4-methyl-pentanoic acid methyl ester (80 mg, 0.18 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, and extracted with CH2Cl2 (3×). The organic layer was washed with brine, dried over Na2SO4, filtered and evaporated. The residue was purified by chromatography (5-25% ethyl acetate in CH2Cl2) to give the product as a white foam (60 mg, 77%). 1H NMR (300 MHz, CDCl3) δ 8.21 (d, J=8.29 Hz, 2H), 8.05-8.15 (m, 2H), 7.73 (d, J=8.29 Hz, 2H), 7.65 (d, J=1.51 Hz, 2H), 7.11-7.23 (m, 2H), 3.80 (t, J=7.72 Hz, 1H), 2.08-2.16 (m, 1H), 1.77 (dt, J=7.06, 13.75 Hz, 1H), 1.48-1.64 (m, 1H), 0.96 (d, J=6.40 Hz, 6H). MS m/e 432.3 (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 (5-25% ethyl acetate in CH2Cl2)

Sources & evidence

ORD record
ord-6bc6aa31e9434a3e8c3ff1608fa8a342
Source dataset
uspto-grants-2011_06
Patent number
US07968725B2

Reaction notes

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