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

HRID 735476노트

반응식

HRID 735476 반응식
[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

참가 물질

14

반응물 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

생성물 1

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

시약·촉매·용매 5

HCID 180Acetone용매HCID 887Methanol용매HCID 962Water용매HCID 5943Carbon Tetrachloride용매HCID 8028Tetrahydrofuran용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-fc50c52819ac41529dd480ecaa0f587f
출처 데이터셋
uspto-grants-2009_09
특허 번호
US07592363B2

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