Sulfuric Acid → 1-[4-({3-[2-Benzyl-7-(trifluoromethyl)-2H-indazol-3-YL]phenoxy}methyl)phenyl]cyclopentanecarboxylic acid

HRID 735476Notes

Reaction equation

HRID 735476 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]([C:32]1([C:37]2[CH:42]=[CH:41][C:40]([CH2:43]Br)=[CH:39][CH:38]=2)[CH2:36][CH2:35][CH2:34][CH2:33]1)=[O:31].C(=O)([O-])[O-].[K+].[K+].C1(C)C=CC(C2(C(O)=O)CCCC2)=CC=1.S(=O)(=O)(O)O.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.C(Cl)(Cl)(Cl)Cl.C1COCC1.O>[CH2:1]([N:8]1[C:16]([C:17]2[CH:18]=[C:19]([CH:20]=[CH:21][CH:22]=2)[O:23][CH2:43][C:40]2[CH:39]=[CH:38][C:37]([C:32]3([C:30]([OH:31])=[O:29])[CH2:36][CH2:35][CH2:34][CH2:33]3)=[CH:42][CH:41]=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

14

Reactant 8

HCID 1118Sulfuric AcidHCID 3939Lithium HydroxideHCID 7187Benzoyl PeroxideHCID 11430Potassium CarbonateHCID 67184N-bromobutanimideHCID 986221-(4-Methylphenyl)cyclopentanecarboxylic acidHCID 116175953-(2-Benzyl-7-trifluoromethyl-2H-indazol-3-yl)-phenolHCID 670211981-(4-Bromomethyl-phenyl)-cyclopentanecarboxylic acid methyl ester

Product 1

HCID 670211771-[4-({3-[2-Benzyl-7-(trifluoromethyl)-2H-indazol-3-YL]phenoxy}methyl)phenyl]cyclopentanecarboxylic acid

Reagents, catalysts & solvents 5

HCID 180AcetoneSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 5943Carbon TetrachlorideSolventHCID 8028TetrahydrofuranSolvent

Procedure

This compound was prepared similarly to that of Example 525 by treating 3-(2-benzyl-7-trifluoromethyl-2H-indazole-3-yl)-phenol (20 mg, 1 eq) with 1-(4-bromomethyl-phenyl)-cyclopentanecarboxylic acid methyl ester (48 mg, 3 eq) and potassium carbonate (37 mg, 5 eq) in acetone (1.5 mL). The latter reagent was obtained by heating 1-p-tolyl-cyclopentanecarboxylic acid in methanol and a catalytic amount of sulphuric acid. Subsequent α-bromination was accomplished by refluxing the ester (100 mg, 1 eq) with NBS (82 mg, 1 eq) and benzoyl peroxide (5 mg, 3%) in carbon tetrachloride (2 mL) for one hour. 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 hydrolyzed with aq LiOH (1M, 40 eq)/THF 1:1 and purified by preparative HPLC, affording the desired product in 48% 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
  6. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-fc50c52819ac41529dd480ecaa0f587f
Source dataset
uspto-grants-2009_09
Patent number
US07592363B2

Reaction notes

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