Cesium carbonate → (S)-1-[3-(1-Methyl-1H-benzoimidazol-2-yl)-phenyl]-piperidine-3-carboxylic acid ethyl ester

HRID 77066

反応式

HRID 77066 の反応式
Br[C:2]1[CH:3]=[C:4]([C:8]2[N:12]([CH3:13])[C:11]3[CH:14]=[CH:15][CH:16]=[CH:17][C:10]=3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[CH2:18]([O:20][C:21](=[O:28])[C@H:22]1[CH2:27][CH2:26][CH2:25][NH:24][CH2:23]1)[CH3:19].C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[CH2:18]([O:20][C:21]([C@H:22]1[CH2:27][CH2:26][CH2:25][N:24]([C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([C:8]3[N:12]([CH3:13])[C:11]4[CH:14]=[CH:15][CH:16]=[CH:17][C:10]=4[N:9]=3)[CH:3]=2)[CH2:23]1)=[O:28])[CH3:19]

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 187784Ethyl (3S)-piperidine-3-carboxylateHCID 634876Binap, (A+-)-HCID 9624512-(3-bromophenyl)-1-methyl-1H-benzimidazole

生成物 1

HCID 66977654(S)-1-[3-(1-Methyl-1H-benzoimidazol-2-yl)-phenyl]-piperidine-3-carboxylic acid ethyl ester収率 70%

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 1—Step c 2-(3-Bromo-phenyl)-1-methyl-1H-benzoimidazole (0.85 g, 2.96 mmol), (S)-(+)-Nipecotic acid ethyl ester (0.60 g, 3.85 mmol) and cesium carbonate (4.82 g, 14.80 mmol) were placed into a dry Schlenk tube under nitrogen. At the same time palladium acetate (0.14 g, 0.60 mmol), and rac-2,2′bis(diphenylphosphino)-1,1′-binaphtyl (BINAP) (0.57 g, 0.90 mmol) were placed into a dry 7 mL vial under nitrogen. Then dry toluene (5 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, filtered off, and the insoluble material was washed with EtOAC (3×10 mL). The organic solution was concentrated under reduced pressure and crude was purified by flash chromatography (eluent: cyclohexane:AcOEt gradient from 100% of cyclohexane to cyclohexane 4:AcOEt 1) to afford 0.75 g of the title compound (70%).

後処理

  1. additionbefore being added to the first flask
  2. temperaturecooled to room temperature
  3. filtrationfiltered off
  4. washthe insoluble material was washed with EtOAC (3×10 mL)
  5. concentrationThe organic solution was concentrated under reduced pressure and crude
  6. customwas purified by flash chromatography (eluent: cyclohexane:AcOEt gradient from 100% of cyclohexane to cyclohexane 4:AcOEt 1)

出典と根拠

ORDレコード
ord-89a0edb05816463b8880ff3ddfc76274
出典データセット
uspto-grants-2014_09
特許番号
US08835648B2

関連ノート

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