Cesium carbonate → 2-[2-Chloro-5-(4-ethoxycarbonyl-piperidin-1-yl)-phenyl]-5-fluoro benzoimidazole-1-carboxylic acid tert-butyl ester

HRID 77074노트

반응식

HRID 77074 반응식
[C:1]([O:5][C:6]([N:8]1[C:12]2[CH:13]=[CH:14][C:15]([F:17])=[CH:16][C:11]=2[N:10]=[C:9]1[C:18]1[CH:23]=[C:22](Br)[CH:21]=[CH:20][C:19]=1[Cl:25])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:26]([O:28][C:29]([CH:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1)=[O:30])[CH3:27].C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[C:12]2[CH:13]=[CH:14][C:15]([F:17])=[CH:16][C:11]=2[N:10]=[C:9]1[C:18]1[CH:23]=[C:22]([N:34]2[CH2:35][CH2:36][CH:31]([C:29]([O:28][CH2:26][CH3:27])=[O:30])[CH2:32][CH2:33]2)[CH:21]=[CH:20][C:19]=1[Cl:25])=[O:7])([CH3:4])([CH3:3])[CH3:2]

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 70770Ethyl 4-piperidinecarboxylateHCID 634876Binap, (A+-)-HCID 669779322-(5-Bromo-2-chloro-phenyl)-5-fluoro-benzoimidazole-1-carboxylic acid tert-butyl ester

생성물 1

HCID 669774172-[2-Chloro-5-(4-ethoxycarbonyl-piperidin-1-yl)-phenyl]-5-fluoro benzoimidazole-1-carboxylic acid tert-butyl ester수율 68%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 1140Toluene용매

반응 조건

온도
80 °C

실험 절차

Method 3,4—Step d 2-(5-Bromo-2-chloro-phenyl)-5-fluoro-benzoimidazole-1-carboxylic acid tert-butyl ester (1.04 g, 2.46 mmol), piperidine-4-carboxylic acid ethyl ester (0.49 mL, 3.19 mmol) and cesium carbonate (3.99 g, 12.29 mmol) were placed into a dry Schlenk tube under nitrogen. At the same time palladium acetate (0.11 g, 0.49 mmol), and BINAP (0.46 g, 0.74 mmol) were placed into a dry 7 mL vial under nitrogen. Then dry toluene (4 mL) was added and the mixture was stirred 20 minutes under nitrogen before being added to the first flask. The reaction mixture was heated at 80° C. overnight, cooled to room temperature, salts were filtered off, the organic solution was concentrated under reduced pressure and crude was purified by flash chromatography (eluent: cyclohexane:AcOEt gradient from cyclohexane:AcOEt/5:1 to 1:2) to afford 0.84 g of the title compound (68%).

후처리

  1. additionbefore being added to the first flask
  2. temperaturecooled to room temperature
  3. filtrationsalts were filtered off
  4. concentrationthe organic solution was concentrated under reduced pressure and crude
  5. customwas purified by flash chromatography (eluent: cyclohexane:AcOEt gradient from cyclohexane:AcOEt/5:1 to 1:2)

출처 및 근거

ORD 기록
ord-8626708b0d0c4a58b20cbe8cb8fb5817
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08835648B2

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