Hydrochloric Acid → 6-(4-Hydroxy-2-methyl-phenyl)-1-isopropyl-2-methyl-1H-indole-3-carboxylic acid methyl ester

HRID 250255노트

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HRID 250255 반응식
[CH3:1][O:2][C:3]([C:5]1[C:13]2[C:8](=[CH:9][C:10](Cl)=[CH:11][CH:12]=2)[N:7]([CH:15]([CH3:17])[CH3:16])[C:6]=1[CH3:18])=[O:4].[CH3:19][C:20]1[CH:21]=[C:22]([OH:35])[CH:23]=[CH:24][C:25]=1B1OC(C)(C)C(C)(C)O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].Cl>O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.O1CCOCC1>[CH3:1][O:2][C:3]([C:5]1[C:13]2[C:8](=[CH:9][C:10]([C:25]3[CH:24]=[CH:23][C:22]([OH:35])=[CH:21][C:20]=3[CH3:19])=[CH:11][CH:12]=2)[N:7]([CH:15]([CH3:17])[CH3:16])[C:6]=1[CH3:18])=[O:4]

참가 물질

9

반응물 4

HCID 313Hydrochloric AcidHCID 62657Potassium Phosphate, TribasicHCID 574432723-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 672714736-Chloro-1-isopropyl-2-methyl-1H-indole-3-carboxylic acid methyl ester

생성물 1

HCID 672718996-(4-Hydroxy-2-methyl-phenyl)-1-isopropyl-2-methyl-1H-indole-3-carboxylic acid methyl ester수율 88.1%

시약·촉매·용매 4

HCID 75806Tricyclohexylphosphine촉매HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 312751,4-Dioxane용매

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온도
120 °C

실험 절차

A mixture of 6-chloro-1-isopropyl-2-methyl-1H-indole-3-carboxylic acid methyl ester (200 mg, 0.75 mmol), 3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenol (351 mg, 1.50 mmol), dioxane (2.5 mL), potassium phosphate tribasic, N-hydrate (2.59 g, 1.28 mmol), tris(dibenzylideneacetone)dipalladium(0) (12 mg, 0.013 mmol) and tricyclohexylphosphine (9 mg, 0.03 mmol) is stirred under nitrogen at 120° C. for 16 h. The mixture is acidified with 1N HCl, diluted with water, and extracted with ether. The combined ether layers are washed with brine and dried over MgSO4. The crude product is purified via flash chromatography (40 g SiO2) cluting with 30% THF-heptane to yield the title compound (223 mg, 88%) as a white solid. ES/MS ma/c 338.0 (M+1).

후처리

  1. extractionextracted with ether
  2. washThe combined ether layers are washed with brine
  3. dry with materialdried over MgSO4
  4. customThe crude product is purified via flash chromatography (40 g SiO2)

출처 및 근거

ORD 기록
ord-1b982d3c3d99461c8e50912a92b917fa
출처 데이터셋
uspto-grants-2011_01
특허 번호
US07863302B2

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