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Toluene → Methyl 6-chloro-5-(4-(1-hydroxy-2-methylpropan-2-yl)-3-methoxyphenyl)-1H-indole-3-carboxylate

HRID 1054724
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HRID 1054724 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:12])([CH3:11])[CH2:9][OH:10])=[C:4]([O:13][CH3:14])[CH:3]=1.[Cl:15][C:16]1[CH:24]=[C:23]2[C:19]([C:20]([C:25]([O:27][CH3:28])=[O:26])=[CH:21][NH:22]2)=[CH:18][C:17]=1B1OCC(C)(C)CO1.C(=O)([O-])[O-].[K+].[K+].C1(C)C=CC=CC=1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C1COCC1.O.C(O)C>[Cl:15][C:16]1[CH:24]=[C:23]2[C:19]([C:20]([C:25]([O:27][CH3:28])=[O:26])=[CH:21][NH:22]2)=[CH:18][C:17]=1[C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:12])([CH3:11])[CH2:9][OH:10])=[C:4]([O:13][CH3:14])[CH:3]=1
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참가 물질

9

반응물 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 86698665methyl 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylateHCID 866987222-(4-Bromo-2-methoxyphenyl)-2-methylpropan-1-ol2회

생성물 1

HCID 86698724Methyl 6-chloro-5-(4-(1-hydroxy-2-methylpropan-2-yl)-3-methoxyphenyl)-1H-indole-3-carboxylate수율 56%

시약·촉매·용매 4

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 702Ethanol용매HCID 962Water용매HCID 8028Tetrahydrofuran용매

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온도
115 °C

실험 절차

A mixture of 2-(4-bromo-2-methoxyphenyl)-2-methylpropan-1-ol (crude product from Step 4, containing 40% of the desired material, 75 mg, 0.12 mmol), methyl 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylate (45 mg, 0.14 mmol), PdCl2(dppf) (11 mg, 0.013 mmol), potassium carbonate (80 mg, 0.58 mmol), toluene (0.6 mL), ethanol (0.3 mL), water (0.3 mL), and THF (0.3 mL) was stirred at 115° C. for 2.5 hours. The reaction mixture was cooled to room temperature and extracted with ethyl acetate (4 mL) of ethyl acetate. The extract was loaded on silica gel. Chromatography on a silica gel column, eluting with a gradient from 10% to 40% of ethyl acetate in heptane gave the title compound (25 mg, 56% yield). MS (ES−) 386.2 (M−H)−. Retention time: 3.38 min. Column: Phenomenex Gemini-NX, 4.6 mm×50 mm, C18, 3 μm, 110A; Column Temperature 60° C. Mobile Phase A: 0.1% formic acid in water (v/v); Mobile Phase B: 0.1% formic acid in acetonitrile (v/v) Gradient Profile: Flow-1.5 mL/min. Initial conditions: A-95%, B-5%; Linear Ramp to A-0%, B-100% over 0.0-4.10 min; hold at A-0%, B-100% from 4.10-4.50 min; return to initial conditions 4.60-5.0 min.

후처리

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted with ethyl acetate (4 mL) of ethyl acetate
  3. washChromatography on a silica gel column, eluting with a gradient from 10% to 40% of ethyl acetate in heptane

출처 및 근거

ORD 기록
ord-6b230829c98a4a32a6a0aa614d8b5c45
출처 데이터셋
uspto-grants-2016_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09394285B2

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