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

HRID 77074ノート

反応式

HRID 77074 の反応式
[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]

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 1140Toluene溶媒

反応条件

温度
80 °C

実験手順

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%).

後処理

  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)

出典と根拠

ORDレコード
ord-8626708b0d0c4a58b20cbe8cb8fb5817
出典データセット
uspto-grants-2014_09
特許番号
US08835648B2

反応ノート

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