Sulfuric Acid → 2-[4-({3-[2-Benzyl-7-(trifluoromethyl)-2H-indazol-3-YL]phenoxy}methyl)phenyl]-2-methylpropanoic acid

HRID 735477Notes

Reaction equation

HRID 735477 reaction equation
[CH2:1]([N:8]1[C:16]([C:17]2[CH:18]=[C:19]([OH:23])[CH:20]=[CH:21][CH:22]=2)=[C:15]2[C:10]([C:11]([C:24]([F:27])([F:26])[F:25])=[CH:12][CH:13]=[CH:14]2)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[O:29][C:30](=[O:42])[C:31]([C:34]1[CH:39]=[CH:38][C:37]([CH2:40]Br)=[CH:36][CH:35]=1)([CH3:33])[CH3:32].C(=O)([O-])[O-].[K+].[K+].C1(C)C=CC(CC(O)=O)=CC=1.S(=O)(=O)(O)O.[H-].[Na+].CI.C1C(=O)N(Br)C(=O)C1.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.[Li+].[OH-]>CC(C)=O.CO.C1COCC1.C(Cl)(Cl)(Cl)Cl.O>[CH2:1]([N:8]1[C:16]([C:17]2[CH:18]=[C:19]([CH:20]=[CH:21][CH:22]=2)[O:23][CH2:40][C:37]2[CH:36]=[CH:35][C:34]([C:31]([CH3:33])([CH3:32])[C:30]([OH:42])=[O:29])=[CH:39][CH:38]=2)=[C:15]2[C:10]([C:11]([C:24]([F:27])([F:25])[F:26])=[CH:12][CH:13]=[CH:14]2)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

16

Reactant 10

HCID 1118Sulfuric AcidHCID 3939Lithium HydroxideHCID 6328Methyl iodideHCID 7187Benzoyl PeroxideHCID 11430Potassium CarbonateHCID 24758Sodium hydrideHCID 67184N-bromobutanimideHCID 248474p-Tolylacetic acidHCID 116175953-(2-Benzyl-7-trifluoromethyl-2H-indazol-3-yl)-phenolHCID 18423131Methyl 2-(4-(bromomethyl)phenyl)-2-methylpropanoate

Product 1

HCID 670210122-[4-({3-[2-Benzyl-7-(trifluoromethyl)-2H-indazol-3-YL]phenoxy}methyl)phenyl]-2-methylpropanoic acid

Reagents, catalysts & solvents 5

HCID 180AcetoneSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 5943Carbon TetrachlorideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

This compound was prepared similarly to that of Example 525 by treating 3-(2-benzyl-7-trifluoromethyl-2H-indazole-3-yl)-phenol (23 mg, 1 eq) with 2-(4-bromomethyl-phenyl)-2-methyl-propionic acid methyl ester (17 mg, 1 eq) and potassium carbonate (26 mg, 3 eq) in acetone (2 mL). The latter reagent was obtained by heating p-tolyl-acetic acid in methanol and a catalytic amount of sulphuric acid. Subsequent methylation was accomplished by treating the obtained ester (50 mg, 1 eq) with sodium hydride (26 mg, 2.2 eq) and methyl iodide (41 μL, 2.2 eq) in THF (1 mL). Then α-bromination was accomplished by refluxing the ester (16 mg, 1 eq) with NBS (15 mg, 1 eq) and benzoyl peroxide (1 mg, 3%) in carbon tetrachloride (1.5 mL) overnight. The reaction mixture was cooled, water was added and product extracted with dichloromethane. The residue was purified by flash chromatography (ethyl acetate/n-heptane, 1:9, as an eluent). Then the resulting compound was then hydrolyzed with aq LiOH (1M, 40 eq)/THF, 1:1, and purified by preparative HPLC, affording the desired product in 26% yleld.

Workup

  1. customThis compound was prepared similarly to that of Example 525
  2. customThe latter reagent was obtained
  3. temperatureThe reaction mixture was cooled
  4. extractionproduct extracted with dichloromethane
  5. customThe residue was purified by flash chromatography (ethyl acetate/n-heptane, 1:9

Sources & evidence

ORD record
ord-0e1d5f7165894db58aabb7cce5e7a352
Source dataset
uspto-grants-2009_09
Patent number
US07592363B2

Reaction notes

Loading…