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

HRID 735476Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 735476
[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

Komponenten

14

Edukt 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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 180AcetoneLösungsmittelHCID 887MethanolLösungsmittelHCID 962WaterLösungsmittelHCID 5943Carbon TetrachlorideLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-fc50c52819ac41529dd480ecaa0f587f
Quelldatensatz
uspto-grants-2009_09
Patentnummer
US07592363B2

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