Toluene → 4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorobenzoic acid

HRID 83893Notes

Reaction equation

HRID 83893 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:11]2[N:15]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[C:14]([S:23][CH2:24][C:25]3[C:37]([F:38])=[CH:36][C:28]([C:29]([O:31]C(C)(C)C)=[O:30])=[CH:27][C:26]=3[F:39])=[N:13][CH:12]=2)([CH3:10])[CH3:9])=[CH:4][C:3]=1[O:40][CH3:41].C(O)(C(F)(F)F)=O.C1(C)C=CC=CC=1>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:11]2[N:15]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[C:14]([S:23][CH2:24][C:25]3[C:26]([F:39])=[CH:27][C:28]([C:29]([OH:31])=[O:30])=[CH:36][C:37]=3[F:38])=[N:13][CH:12]=2)([CH3:10])[CH3:9])=[CH:4][C:3]=1[O:40][CH3:41]

Participants

5

Reactant 3

HCID 1140TolueneHCID 6422Trifluoroacetic acidHCID 66740019tert-butyl 4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorobenzoate

Product 1

HCID 667403914-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorobenzoic acidYield 100,550.602%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorobenzoate (95 g, 0.16 mmol) in CH2Cl2 (500 mL) at 0° C. was added TFA (500 mL) and then was stirred at room temperature. After 3 h, the reaction mixture was evaporated and the residue was diluted with CH2Cl2(1.5 L), washed with water (600 mL×2). To the organic layers more water (600 mL) was added, it was neutralized with slow addition of aq. NaHCO3 solution and organic layer was separated. Water (600 mL) was added to the organic layer and adjusted aqueous layer to pH 3-4 with 1N HCl. The organic layer was separated, dried over MgSO4, filtered and concentrated under reduced pressure to give a residue. Toluene (600 mL) was added to the residue and the solution was evaporated and same process was repeated one more time to give the title compound as a white solid (88 g, quant). 1H NMR (400 MHz, CDCl3) δ 7.55 (s, 1H), 7.46-7.49 (d, 2H), 7.16-7.19 (m, 1H), 6.92-6.97 (t, 2H), 6.69-6.71 (t, 2H), 6.62 (s, 1H), 6.49-6.51 (d, 1H), 3.84 (s, 3H), 3.53 (s, 2H), 1.58 (s, 6H); MS (EI) m/z 547 (MH+).

Workup

  1. customthe reaction mixture was evaporated
  2. additionthe residue was diluted with CH2Cl2(1.5 L)
  3. washwashed with water (600 mL×2)
  4. additionTo the organic layers more water (600 mL) was added
  5. additionit was neutralized with slow addition of aq. NaHCO3 solution and organic layer
  6. customwas separated
  7. additionWater (600 mL) was added to the organic layer and adjusted aqueous layer to pH 3-4 with 1N HCl
  8. customThe organic layer was separated
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customto give a residue
  13. customthe solution was evaporated

Sources & evidence

ORD record
ord-8f3f1efce04343fba64603f31da1cd4b
Source dataset
uspto-grants-2014_09
Patent number
US08846739B2

Reaction notes

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